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Park, Juin, Woo Sun Kwon, Sun Kyoung Kang, Tae Soo Kim, Jihyun Hwang, Sang Woo Cho, Kyunggon Kim, Hyun Cheol Chung, and Sun Young Rha. "Abstract 5079: Comparative proteome analysis for predicting the prognosis of trastuzumab-based therapy." Cancer Research 82, no. 12_Supplement (June 15, 2022): 5079. http://dx.doi.org/10.1158/1538-7445.am2022-5079.
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Abstract Trastuzumab, a HER2-targeting antibody, has markedly altered the clinical course of the disease in HER2 + gastric cancer, which is 10-15% of metastatic GC. However, the majority of patients develop resistance within one year of treatment. Therefore, understanding the mechanisms of trastuzumab resistance is urgently needed to overcome trastuzumab resistance. This study explored the characteristics of trastuzumab resistant cell lines through comparative proteome analysis. We previously reported establishment of four trastuzumab resistant cell lines from HER2 amplified GC cell lines by trastuzumab dose-escalation treatment; YCC-33TR, YCC-38TR, NCI-N87TR, and SNU-216TR. Formalin-fixed paraffin-embedded tissue samples were obtained 10 GC patients prior to trastuzumab therapy. The patients were first stratified into poor and good responders based on whether their tumors had or had not progressed. For analysis of differentially expressed proteins (DEPs), label-free quantitative proteomic profiling was performed using high-resolution LC-MS system. Gene ontology (GO) and KEGG pathway enrichment analyses were conducted using DAVID database. Consistent with the previous results, we found that HER2 expression in TR cell lines remained as high as parental cell lines, also in proteomic profiling. As a result of proteomic analysis, total 5285 proteins were identified in 4 parental and 4 TR cell lines; 4854 common proteins, while 55 proteins unique to parental cell lines and 58 proteins unique to TR cell lines. Then, we did the hierarchical clustering with these DEPs to identify protein expression patterns. We observed that 129 and 62 proteins were upregulated in parental and TR cell lines, respectively (p<0.05). We identified C5orf51 and CENP-E, poor prognostic factors, were upregulated 200-fold in TR cell lines. Interestingly, we found that HLA-B, ITM2C, and PPP1R3D were highly expressed in TR cell lines and trastuzumab poor responders. In conclusion, we performed comparative proteome analysis in parental and TR cell lines and investigated the corresponding expression change. It may gain further novel insights into the mechanisms of trastuzuamb resistance. Citation Format: Juin Park, Woo Sun Kwon, Sun Kyoung Kang, Tae Soo Kim, Jihyun Hwang, Sang Woo Cho, Kyunggon Kim, Hyun Cheol Chung, Sun Young Rha. Comparative proteome analysis for predicting the prognosis of trastuzumab-based therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5079.
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Oca??a, Alberto, Juan J. Cruz, and Atanasio Pandiella. "Trastuzumab and Antiestrogen Therapy." American Journal of Clinical Oncology 29, no. 1 (February 2006): 90–95. http://dx.doi.org/10.1097/01.coc.0000190274.00570.0a.
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Ebb, David, Paul Meyers, Holcombe Grier, Mark Bernstein, Richard Gorlick, Steven E. Lipshultz, Mark Krailo, et al. "Phase II Trial of Trastuzumab in Combination With Cytotoxic Chemotherapy for Treatment of Metastatic Osteosarcoma With Human Epidermal Growth Factor Receptor 2 Overexpression: A Report From the Children's Oncology Group." Journal of Clinical Oncology 30, no. 20 (July 10, 2012): 2545–51. http://dx.doi.org/10.1200/jco.2011.37.4546.
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PurposeDespite efforts to intensify chemotherapy, survival for patients with metastatic osteosarcoma remains poor. Overexpression of human epidermal growth factor receptor 2 (HER2) in osteosarcoma has been shown to predict poor therapeutic response and decreased survival. This study tests the safety and feasibility of delivering biologically targeted therapy by combining trastuzumab with standard chemotherapy in patients with metastatic osteosarcoma and HER2 overexpression.Patients and MethodsAmong 96 evaluable patients with newly diagnosed metastatic osteosarcoma, 41 had tumors that were HER2-positive by immunohistochemistry. All patients received chemotherapy with cisplatin, doxorubicin, methotrexate, ifosfamide, and etoposide. Dexrazoxane was administered with doxorubicin to minimize the risk of cardiotoxicity from treatment with trastuzumab and anthracycline. Only patients with HER2 overexpression received concurrent therapy with trastuzumab given for 34 consecutive weeks.ResultsThe 30-month event-free and overall survival rates for patients with HER2 overexpression treated with chemotherapy and trastuzumab were 32% and 59%, respectively. For patients without HER2 overexpression, treated with chemotherapy alone, the 30-month event-free and overall survival rates were 32% and 50%, respectively. There was no clinically significant short-term cardiotoxicity in patients treated with trastuzumab and doxorubicin.ConclusionDespite intensive chemotherapy plus trastuzumab for patients with HER2-positive disease, the outcome for all patients was poor, with no significant difference between the HER2-positive and HER2-negative groups. Although our findings suggest that trastuzumab can be safely delivered in combination with anthracycline-based chemotherapy and dexrazoxane, its therapeutic benefit remains uncertain. Definitive assessment of trastuzumab's potential role in treating osteosarcoma would require a randomized study of patients with HER2-positive disease.
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Dormann, Clemens. "Metastatic Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Current Treatment Standards and Future Perspectives." Breast Care 15, no. 6 (2020): 570–78. http://dx.doi.org/10.1159/000512328.
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<b><i>Background:</i></b> The basis of improved systemic therapy for inoperable or metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer is formed by HER2-targeting monoclonal antibodies. Dual HER2 blockade with pertuzumab and trastuzumab in combination with docetaxel in previously untreated patients, and trastuzumab emtansine (T-DM1, an antibody-drug conjugate [ADC] consisting of trastuzumab, a linker and a cytotoxic payload) after prior trastuzumab therapy have demonstrated progression-free survival (PFS) and overall survival (OS) superior to what was achieved with the previous treatment routine. Therefore, pertuzumab and trastuzumab with chemotherapy (preferably with a taxane) and T-DM1 are considered the current standard of care in the first- and second-line settings, respectively. For later lines of therapy, no uniformly recognized standard of care has been defined. Accepted options include treatment with trastuzumab beyond progression, in combination with a broad variety of single-agent chemotherapies used sequentially, or lapatinib (an HER2-targeting tyrosine kinase inhibitor [TKI]) in combination with either trastuzumab or capecitabine. However, most of these options have not been formally tested in patients receiving the current standard of care therapy for metastatic disease. <b><i>Summary:</i></b> In patients previously treated with today’s standard of care, including a significant subgroup with untreated or progressing brain metastases, the combination of tucatinib, a novel HER2-targeting TKI, with trastuzumab and capecitabine, demonstrates a clinically meaningful improvement in PFS and OS when compared to placebo with trastuzumab and capecitabine. Neratinib, another HER2 TKI, in combination with capecitabine, compared to lapatinib and capecitabine, as well as margetuximab, an HER2-directed monoclonal antibody with a fragment c (Fc) domain engineered to enhance immune activation, compared to trastuzumab, both combined with the investigator’s choice of chemotherapy, showed a statistically significantly longer PFS. However, not all patients in the respective trials had received pertuzumab and T-DM1 prior to enrollment and, so far, no improvement in OS has been demonstrated. After a median of 6 prior lines of therapy, trastuzumab deruxtecan (T-DXd), a novel ADC, showed a meaningful overall response and PFS. Although the safety profile was generally manageable, treatment-related interstitial lung disease (ILD) might pose a challenge in routine practice. Pyrotinib, another HER2 TKI, was evaluated in combination with capecitabine in patients after prior exposure to trastuzumab when pertuzumab and T-DM1 were not available. In this setting, PFS was better than with lapatinib and capecitabine. <b><i>Key Messages:</i></b> In 2020, pertuzumab and trastuzumab with taxane-based chemotherapy in the first line, and T-DM1 in the second line, remain the standard of care. Tucatinib, neratinib, margetuximab, and T-DXd expand the armamentarium for treatment beyond the second line. Pyrotinib might be another option, especially for patients, who do not have access to pertuzumab and T-DM1.
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Lee, S. W., H. F. Kamaruzaman, and J. Sabirin. "Trastuzumab as An Adjuvant Therapy for Early Breast Cancer." Journal of Global Oncology 4, Supplement 2 (October 1, 2018): 70s. http://dx.doi.org/10.1200/jgo.18.31500.
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Background: In Malaysia, breast cancer is the most common cancer in females and also the first most common cancer among population regardless of gender. Trastuzumab is used for the treatment of early-stage breast cancer that is HER2 positive. Although this treatment has been routinely used, there are still controversial on the duration of the addition of trastuzumab to the chemotherapy regimen. Aim: To assess the safety and effectiveness of trastuzumab as an adjuvant in early breast cancer patients through a systematic review. Methods: Electronic databases were searched through the Ovid interface. The titles and abstracts were screened against the inclusion and exclusion criteria and then evaluated the selected full-text articles. Results: There was high level of evidence to suggest that the risk of congestive heart failure (CHF) was significantly higher in patients treated with trastuzumab compared with nontrastuzumab control group (RR 5.11; 90% CI: 3.00-8.72, P < 0.00001) in one Cochrane review, (RR 3.19; 95% CI: 2.03-5.02, P < 0.00001) in one systematic review and meta-analysis. Evidence also suggested that the risk was significantly higher with longer duration of treatment (> 6 months) RR 5.39; 90% CI: 3.56-8.17, P < 0.00001. The overall survival (OS) significantly favored trastuzumab-containing regimen over nontrastuzumab control group, (HR 0.66; 95% CI: 0.55-0.77, P < 0.00001). In terms of duration, subgroup analysis reported that the overall survival (OS) significantly favored trastuzumab-containing regimen over nontrastuzumab control group trials where trastuzumab was given longer (> 6 months), HR 0.67; 95% CI: 0.57-0.80, P < 0.00001. In the trials that gave trastuzumab and chemotherapy concurrently, HR significantly favored trastuzumab-containing regimens (HR 0.64; 95% CI: 0.57-0.80, P < 0.00001). The evidence from Cochrane systematic review suggests that disease-free survival (DFS) favored trastuzumab-containing regimen over the nontrastuzumab control group (HR 0.60; 95% CI: 0.50-0.71, P < 0.00001). In terms of duration of treatment, there was no significant difference in DFS when trastuzumab was used for less than six months or more than six months. The DFS significantly favored trastuzumab-containing regimen over nontrastuzumab control group when used either concurrently or sequentially. Limited evidence to suggest that two years duration of adjuvant trastuzumab was not more effective that one year of treatment. However, six months treatment with trastuzumab failed to show that it was noninferior to twelve months of trastuzumab. There was limited retrievable evidence to suggest that there is no significant difference in OS and DFS between the twelve months regimen and 9-week regimen for trastuzumab. Conclusion: Despite the higher rates of cardiac events, twelve months of adjuvant trastuzumab was suggested as the standard of care. However, other issues including cost and cost-effectiveness should be considered.
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Gabric, Ivo Darko, Ljubica Vazdar, Hrvoje Pintaric, Danijel Planinc, Robert Separovic, Mario Stefanovic, Matias Trbusic, Marijana Jazvic, Ozren Vinter, and Zeljko Soldic. "Cardiotoxicity caused by trastuzumab therapy." Cardiologia Croatica 9, no. 9-10 (October 29, 2014): 433. http://dx.doi.org/10.15836/ccar.2014.433.
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Brann, Alison M., Melody A. Cobleigh, and Tochi M. Okwuosa. "Cardiovascular Monitoring With Trastuzumab Therapy." JAMA Oncology 2, no. 9 (September 1, 2016): 1123. http://dx.doi.org/10.1001/jamaoncol.2016.1288.
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Keene, K. S., L. C. Klepczyk, R. Meredith, A. Forero-Torres, J. T. Carpenter, H. Krontiras, M. Hyatt, Y. Li, and J. F. De Los Santos. "An update on the dosimetric analysis of concurrent radiation therapy and trastuzumab on early cardiac events." Journal of Clinical Oncology 29, no. 27_suppl (September 20, 2011): 121. http://dx.doi.org/10.1200/jco.2011.29.27_suppl.121.
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121 Background: The impact of radiation therapy (RT) with concurrent trastuzumab on early cardiac morbidity is relatively unknown. Trastuzumab’s radiosensitizing properties may augment both early and late effects of RT. This retrospective review update provides an analysis of cardiac event (CE) development in patients treated with concurrent RT and trastuzumab with a focus on RT heart dose. Methods: Sixty-five patients treated with concurrent RT (30 left, 33 right, 2 bilateral) and trastuzumab at the University of Alabama at Birmingham were identified. Patient data for pre-existing heart disease, cardiac risk factors, drug regimen, and CEs were recorded. Dosimetric parameters of maximum heart dose, mean heart dose, heart volume receiving 5, 10, 15, 20 and 30Gy (V5, V10, V15, V20, V30) were also analyzed. Endpoints include the occurrence of CEs at any time in relation to RT and those specifically after the start of RT. Results: In addition to receiving trastuzumab, 80% of patients received doxorubicin. 15.4% had preexisting heart disease. The mean heart dose for all patients was 248cGy. With a median follow-up of 24.5 months, six patients developed CEs (9.2%), and three of these cases occurred after RT initiation (4, 4, and 0.5 months post-RT). All six CEs occurred during treatment with trastuzumab and consisted of congestive heart failure. Analysis of the heart dose maximum, mean, V5, V10, V15, and V20, V30 were similar in patients with and without CEs, and small differences between groups did not reach statistical significance. CE incidence was significantly associated with smoking (p=0.0037) but not hypertension, diabetes or pre-existing heart disease. Conclusions: This updated retrospective dosimetric analysis did not find a correlation between concurrent trastuzumab and RT on the development of early cardiac events. Modern era RT with 3D conformal planning, the use of heart blocks, and breath hold techniques will continue to decrease the dose to the heart. Longer follow-up will be needed for analysis of the impact of modern technologic advances and late cardiac morbidity.
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Ogawa, Lauren, and Deborah Lindquist. "Dual HER2 Suppression with Lapatinib plus Trastuzumab for Metastatic Inflammatory Breast Cancer: A Case Report of Prolonged Stable Disease." Case Reports in Oncology 11, no. 3 (December 19, 2018): 855–60. http://dx.doi.org/10.1159/000494264.
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Background: Continuous therapy targeting human epidermal growth factor receptor 2 (HER2) is recommended until disease progression for patients with HER2-overexpressing (HER2+) metastatic breast cancer. Prolonged stable disease has been observed with such maintenance therapy using trastuzumab, but the frequency of these cases remains low. Whether combined maintenance therapy with two different HER2-targeted agents could improve the rates of durable progression-free survival compared with trastuzumab alone is under investigation. Objectives: To evaluate the efficacy of the combined HER2-targeted agents, trastuzumab and lapatinib, as maintenance therapy in one patient. Methods: We describe a patient with HER2+, hormone receptor-negative, inflammatory metastatic breast cancer who was previously treated with doxorubicin, cyclophosphamide, and zoledronic acid followed by paclitaxel and trastuzumab. After completion, the patient underwent a bilateral mastectomy and then enrolled into a Phase III open-label clinical trial of trastuzumab plus lapatinib. Results: The patient experienced long-term stable disease on combined lapatinib and trastuzumab maintenance therapy over 4 years. Conclusions: This case demonstrates that prolonged stable disease is possible with lapatinib plus trastuzumab, even in patients with the aggressive inflammatory subtype. Optimization of maintenance therapy could improve outcomes for patients with HER2+ metastatic breast cancer.
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Hassan, Chadi, Florence Correal, Gabriel Vézina, Louise Yelle, and Jean-Philippe Adam. "Safety of trastuzumab after trastuzumab emtansine-induced nodular regenerative hyperplasia: A case report." Journal of Oncology Pharmacy Practice 26, no. 7 (March 19, 2020): 1780–84. http://dx.doi.org/10.1177/1078155220910252.
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Introduction Trastuzumab emtansine is an antibody-drug conjugate targeting the human epidermal growth factor receptor 2 use in recurrent metastatic breast cancer. Cases of trastuzumab emtansine-induced nodular regenerative hyperplasia are often reported as overt noncirrhotic portal hypertension with ascites and variceal bleeding. Case report We report the case of a 61-year-old woman who present multiple stellate angiomas with gradual increased liver transaminases and reduced platelet count during a 27-months course on trastuzumab emtansine therapy for recurrent metastatic breast cancer. After the nodular regenerative hyperplasia was histologically confirmed, the trastuzumab emtansine was stopped. After two months, trastuzumab was restarted together with exemestane. During trastuzumab therapy, the patient had a normalization of liver transaminases, platelet count and a gradual improvement of her stellate angiomas. Trastuzumab was continued for 15 months without any reoccurrence of nodular regenerative hyperplasia. Management and outcome Nodular regenerative hyperplasia should be suspected after one year of trastuzumab emtansine treatment in patients with signs of portal hypertension without cirrhosis. Definitive cessation of trastuzumab emtansine is required after a diagnosis of nodular regenerative hyperplasia and complete resolution of symptoms generally takes several months. Discussion Based on fundamental studies, nodular regenerative hyperplasia is probably caused by the emtansine (DM1) part of the trastuzumab emtansine. It is still unclear if trastuzumab therapy can be reintroduced after nodular regenerative hyperplasia induced by trastuzumab emtansine, depriving the patient of a HER2-targeted therapy. Only one case reported having given trastuzumab in this situation over one month. In our case, trastuzumab was reintroduced without any complications for a long extent following TDM1-associated nodular regenerative hyperplasia.
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Mates, M., G. G. Fletcher, O. C. Freedman, A. Eisen, S. Gandhi, M. Trudeau, and S. F. Dent. "Systemic targeted therapy for her2-positive early female breast cancer: a systematic review of the evidence for the 2014 Cancer Care Ontario systemic therapy guideline." Current Oncology 22 (December 18, 2014): 114. http://dx.doi.org/10.3747/co.22.2322.
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BackgroundThis systematic review addresses the question “What is the optimal targeted therapy for female patients with early-stage human epidermal growth factor receptor 2 (her2)–positive breast cancer?”MethodsThe medline and embase databases were searched for the period January 2008 to May 2014. The Standards and Guidelines Evidence directory of cancer guidelines and the Web sites of major guideline organizations were also searched.ResultsSixty publications relevant to the targeted therapy portion of the systematic review were identified. In four major trials (hera, National Surgical Adjuvant Breast and Bowel Project B-31, North Central Cancer Treatment Group N9831, and Breast Cancer International Research Group 006), adjuvant trastuzumab for 1 year was superior in disease-free survival (dfs) and overall survival (os) to no trastuzumab; trastuzumab showed no benefit in one trial (pacs 04). A shorter duration of trastuzumab (less than 1 year compared with 1 year) was evaluated, with mixed results for dfs: one trial showed superiority (finher), one trial could not demonstrate noninferiority (phare), another trial showed equivalent results (E 2198), and one trial is still ongoing (persephone). Longer trastuzumab duration (hera: 2 years vs. 1 year) showed no improvement in dfs or os and a higher rate of cardiac events. Newer her2-targeted agents (lapatinib, pertuzumab, T-DM1, neratinib) have been or are still being evaluated in both adjuvant and neoadjuvant trials, either by direct comparison with trastuzumab alone or combined with trastuzumab. In the neoadjuvant setting (neoaltto, GeparQuinto, Neosphere), trastuzumab alone or in combination with another anti-her2 agent (lapatinib, pertuzumab) was compared with either lapatinib or pertuzumab alone and showed superior or equivalent rates of pathologic complete response. In the adjuvant setting, lapatinib alone or in combination with trastuzumab, compared with trastuzumab alone (altto) or with placebo (teach), was not superior in dfs. The results of the completed aphinity trial, evaluating the role of dual her2 blockade with trastuzumab and pertuzumab, are highly anticipated. Ongoing trials are evaluating trastuzumab as a single agent without adjuvant chemotherapy (respect) and in patients with low her2 expression (National Surgical Adjuvant Breast and Bowel Project B-47).ConclusionsTaking into consideration disease characteristics and patient preference, 1 year of trastuzumab should be offered to all patients with her2-positive breast cancer who are receiving adjuvant chemotherapy. Cardiac function should be regularly assessed in this patient population.
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Di Lauro, Vincenzo, Elena Torrisi, Ettore Bidoli, Daniela Quitadamo, Sara Cecco, and Andrea Veronesi. "Trastuzumab and Gemcitabine in Pretreated HER2 Overexpressing Metastatic Breast Cancer Patients: Retrospective Analysis of Our Series." Journal of Oncology 2012 (2012): 1–6. http://dx.doi.org/10.1155/2012/198412.
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Trastuzumab-based regimes improved clinical outcome in women with overexpressing HER2 metastatic breast cancer, mainly due to the availability of different combination therapies, clinically active and well tolerated. In this study we retrospectively evaluated clinical activity and toxicity of trastuzuamb plus gemcitabine regimen in heavily pretreated HER2 positive metastatic breast cancer patients. Although the observed population was heavily pretreated, the evaluated regimen was notably effective in terms of response rate, time to progression and survival, with very mild toxicity. These data suggest that in over expressing HER2 metastatic breast cancer patients, sequential trastuzumab based chemotherapeutic regimens can achieve good response rate with prolonged TTP in responding patients, even after other target therapy such as lapatinib based combinations.
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Freedman, Rachel A., Ines Maria Vaz Duarte Luis, Nancy Lin, Joyce Lii, Eric P. Winer, and Nancy Lynn Keating. "Completion of adjuvant trastuzumab for older patients with early-stage breast cancer (BC)." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 616. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.616.
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616 Background: Few data are available about factors associated with completion of adjuvant trastuzumab in older women with BC. We examined rates and predictors of adjuvant trastuzumab completion for older women with early-stage BC. Methods: We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data to identify 1,319 patients ≥66 years with early-stage BC diagnosed between 1999-2007 who received trastuzumab. Completion of trastuzumab was defined as >270 days of therapy. We examined patient, clinical and geographic characteristics associated with trastuzumab completion using multivariable logistic regression. We also assessed rates of hospital admissions for cardiac events during treatment. Results: Most of the 1,319 women were aged ≤76 (70%) and had a comorbidity score=0 (88%); 37% and 23% received anthracyline-taxane-based and taxane-based therapy, respectively, and 16% received trastuzumab without chemotherapy. Overall, 982 women (74.5%) completed trastuzumab. Factors associated with completion are shown below. During treatment, 56 patients (4.2%) had 65 hospital admissions for cardiac events (3.0% in those who completed trastuzumab versus 8.0% in those who did not, p<.001). Conclusions: One-quarter of older patients who initiated adjuvant trastuzumab did not complete therapy. Older women, Hispanic women, those with more comorbidity, and those receiving anthracycline-taxane-based chemotherapy all had lower odds of completion. Rates of hosptializations for cardiac events were higher in those who did not complete therapy. [Table: see text]
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Reeder-Hayes, Katherine, Sharon Peacock Hinton, Ke Meng, Lisa A. Carey, and Stacie B. Dusetzina. "Disparities in Use of Human Epidermal Growth Hormone Receptor 2–Targeted Therapy for Early-Stage Breast Cancer." Journal of Clinical Oncology 34, no. 17 (June 10, 2016): 2003–9. http://dx.doi.org/10.1200/jco.2015.65.8716.
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Purpose Trastuzumab is a key component of adjuvant therapy for stage I to III human epidermal growth factor receptor 2 (HER2)–positive breast cancer. The rates and patterns of trastuzumab use have never been described in a population-based sample. The recent addition of HER2 information to the SEER-Medicare database offers an opportunity to examine patterns of trastuzumab use and to evaluate possible disparities in receipt of trastuzumab. Methods We examined a national cohort of Medicare beneficiaries with incident stage I to III HER2-positive breast cancer diagnosed in 2010 and 2011 (n = 1,362). We used insurance claims data to track any use of trastuzumab in the 12 months after diagnosis as well as to identify chemotherapy drugs used in partnership with trastuzumab. We used modified Poisson regression analysis to evaluate the independent effect of race on likelihood of receiving trastuzumab by controlling for clinical need, comorbidity, and community-level socioeconomic status. Results Overall, 50% of white women and 40% of black women received some trastuzumab therapy. Among women with stage III disease, 74% of whites and 56% of blacks received trastuzumab. After adjustment for tumor characteristics, poverty, and comorbidity, black women were 25% less likely to receive trastuzumab within 1 year of diagnosis than white women (risk ratio, 0.745; 95% CI, 0.60 to 0.93). Conclusion Approxemately one half of patients 65 years of age and older with stage I to III breast cancer do not receive trastuzumab-based therapy, which includes many with locally advanced disease. Significant racial disparities exist in the receipt of this highly effective therapy. Further research that identifies barriers to use and increases uptake of trastuzumab could potentially improve recurrence and survival outcomes in this population, particularly among minority women.
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Krstić, Ivana, Marina Deljanin Ilić, Svetislav Vrbić, and Ivica Pejčić. "Significance of Echocardiography in the Assessment of Left Ventricular Function in Patients Receiving Combined Adjuvant Treatment with Anthracyclines and Trastuzumab / Značaj ehokardiografije u proceni funkcije leve komore kod bolesnica na adjuvantnoj terapji (kombinovana terapija antraciklinima i trastuzumabom)." Acta Facultatis Medicae Naissensis 32, no. 3 (September 1, 2015): 181–87. http://dx.doi.org/10.1515/afmnai-2015-0018.
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Abstract The application of anthracycline and trastuzumab in adjuvant breast cancer treatment approach has significantly improved the survival of patients, but also carries the risk of cardiotoxicity that is manifested by reducing the ejection fraction of the heart. The aim of the study was to investigate the effect of cumulative anthracycline dose in combination therapy with trastuzumab on the left ventricular ejection fraction, and the influence of the time interval for starting the treatment with trastuzumab. The study included a group of 80 breast cancer patients (aged 28 to 75 years) who underwent the therapy with anthracyclines (IV-VI cycles) with the continuation of trastuzumab therapy for a period of one year. Ejection fraction at the end of completing the treatment period (VI anthracycline cycles and trastuzumab) was significantly lower in 68 (93%) patients compared to the value at the beginning of the study (68.2% ± 6.06 to 62.1 ± 6.1%; p <0.0001; difference 6.1%). In five patients (anthracyclines and trastuzumab IV cycles) a decrease of 7.1% EF; p = 0.0043 was registered compared to the baseline values. The reduction in the ejection fraction was highest in patients in whom the trastuzumab therapy was initiated one month after the last anthracycline therapy (7.33%), and lowest in the subgroup who started receiving the therapy after three months (5.31%). In patients on cytostatic therapy, echocardiography proves the reduction in the left ventricular ejection fraction, which is cumulative and dose-dependent, and it also proves that the shorter time interval between the last cycle of anthracycline and the initial trastuzumab treatment the more it is associated with a marked decrease in the left ventricular ejection fraction.
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Tripathy, Debu, Dennis J. Slamon, Melody Cobleigh, Andrew Arnold, Mansoor Saleh, Joanne E. Mortimer, Maureen Murphy, and Stanford J. Stewart. "Safety of Treatment of Metastatic Breast Cancer With Trastuzumab Beyond Disease Progression." Journal of Clinical Oncology 22, no. 6 (March 15, 2004): 1063–70. http://dx.doi.org/10.1200/jco.2004.06.557.
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Purpose In a pivotal phase III trial, the addition of trastuzumab to chemotherapy significantly improved response rate, time to disease progression, and overall survival in women with HER2 overexpressing metastatic breast cancer. We conducted an extension study to this trial to obtain additional safety information and to provide trastuzumab following disease progression. Patients and Methods A total of 247 patients with documented disease progression received weekly intravenous trastuzumab in the extension study. Concurrent therapies were administered at the discretion of the treating physician. Patient groups were based on initial study treatment: chemotherapy alone (group 1, n = 154) or chemotherapy plus trastuzumab (group 2, n = 93). Results Sixty-eight percent of group 1 and 76% of group 2 received chemotherapy plus trastuzumab in the extension trial; the remainder received trastuzumab alone or combined with palliative radiotherapy or hormonal therapy. Seventy-six percent of group 1 and 55% of group 2 experienced at least one adverse event, similar to effects observed in the pivotal trial. Symptomatic or asymptomatic cardiac dysfunction occurred in 9% of group 1 and 2% of group 2 patients. Overall objective response rates were 14% in group 1 and 11% in group 2; median durations of response exceeded 6 months in both groups. Conclusion Our results suggest that prolonged use of trastuzumab therapy is safe and well tolerated. Longer durations of therapy did not appear to increase the risk of cardiac dysfunction. Patients progressing on trastuzumab-containing therapy demonstrate some response to a second trastuzumab-containing regimen. The independent contribution of trastuzumab in this setting merits further study.
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Cortés, Javier, Pierre Fumoleau, Giulia Valeria Bianchi, Teresa M. Petrella, Karen Gelmon, Xavier Pivot, Shailendra Verma, et al. "Pertuzumab Monotherapy After Trastuzumab-Based Treatment and Subsequent Reintroduction of Trastuzumab: Activity and Tolerability in Patients With Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer." Journal of Clinical Oncology 30, no. 14 (May 10, 2012): 1594–600. http://dx.doi.org/10.1200/jco.2011.37.4207.
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Purpose The combination of pertuzumab and trastuzumab resulted in a clinical benefit rate (CBR) of 50% in patients with human epidermal growth factor receptor 2 (HER2) –positive breast cancer whose disease progressed during prior trastuzumab-based therapy. To define whether this previously observed encouraging activity was a result of the combination of pertuzumab and trastuzumab or of pertuzumab alone, we recruited a third cohort of patients who received pertuzumab without trastuzumab. We then investigated the impact of reintroducing trastuzumab to patients whose disease progressed on pertuzumab monotherapy. Patients and Methods Twenty-nine patients with HER2-positive breast cancer whose disease progressed during prior trastuzumab-based therapy received pertuzumab (840 mg loading dose, then 420 mg every 3 weeks) until progressive disease or unacceptable toxicity. Seventeen patients with disease progression continued to receive pertuzumab (at the same dose), with the addition of trastuzumab (4 mg/kg loading dose and then 2 mg/kg weekly or 8 mg/kg loading dose and then 6 mg/kg every 3 weeks). Results All 29 patients enrolled for pertuzumab monotherapy experienced disease progression. The objective response rate (ORR) and CBR were 3.4% and 10.3%, respectively, during pertuzumab monotherapy. With the addition of trastuzumab, the ORR and CBR were 17.6% and 41.2%, respectively. Progression-free survival was longer with combination therapy than pertuzumab monotherapy (17.4 v 7.1 weeks, respectively). Treatment was well tolerated with minimal cardiac dysfunction. Conclusion Although pertuzumab has some activity in patients with HER2-positive breast cancer that progressed during therapy with trastuzumab, the combination of pertuzumab and trastuzumab seems to be more active than monotherapy.
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Waller, Cornelius F., Aleksei Manikhas, Eduardo J. Pennella, Igor Bondarenko, Guzel Mukhametshina, Maria Luisa Abesanis Tiambeng, Charuwan Akewanlop, et al. "Biosimilar trastuzumab-dkst monotherapy versus trastuzumab monotherapy after combination therapy: Final overall survival (OS) from the phase III HERITAGE Trial." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): 1021. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.1021.
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1021 Background: The multicenter, double-blind, randomized, parallel-group, phase 3 Heritage trial (NCT02472964) evaluated efficacy and safety of trastuzumab-dkst (Ogivri), a trastuzumab biosimilar, vs trastuzumab, plus taxane as first-line therapy for patients with HER2+ metastatic breast cancer. Overall response at week (wk) 24 and progression-free survival (PFS) at wk 48 have been reported (Rugo et al, JAMA 2017; ASCO 2018). Methods: Eligible patients were randomized 1:1 to trastuzumab-dkst or trastuzumab, plus taxane. After 24 wks, patients with responding/stable disease continued monotherapy per randomization. Safety and OS during maintenance, cumulative through 36 months of follow-up from last patient on study, are described. Results: 500 patients were randomized; 343 received monotherapy after 24 wks (trastuzumab-dkst, n = 179; trastuzumab, n = 164). 128 patients discontinued monotherapy (trastuzumab-dkst, n = 63; trastuzumab, n = 65); mean time to discontinuation was 19 months in both groups. Treatment-emergent adverse events (TEAEs) during monotherapy were similar for trastuzumab-dkst (69%) and trastuzumab (73%); most were low grade and serious TEAE rates were 6% in both groups. Cumulative rates of TEAEs of special interest were similar for hypersensitivity, pulmonary, and cardiac events (trastuzumab-dkst, 23%, 16%, and 5%; trastuzumab, 24%, 13%, and 5%). Incidences of left ventricular ejection fraction (LVEF) < 50% ≥1 time postbaseline (trastuzumab-dkst, 5%; trastuzumab, 3%) and LVEF < 50% postbaseline and ≥10% reduction (trastuzumab-dkst, 4%; trastuzumab, 3%) were low. At 36 months, 169 patients had received further lines of therapy, with similar distribution of HER2 treatments, endocrine therapies, and chemotherapies. Final median PFS was 11.1 months in both groups. Median duration of response was 9.9 and 9.8 months and median OS was 35.0 and 30.2 months for trastuzumab-dkst and trastuzumab, respectively: unstratified hazard ratio, 0.9 (95% CI, 0.70-1.17). Conclusions: Long-term safety data with similar median OS compared with originator trastuzumab further support the safety and efficacy profile of trastuzumab-dkst. Clinical trial information: NCT02472964.
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Yu, Liuwen, Fangmeng Fu, Jing Li, Meng Huang, Bangwei Zeng, Yuxiang Lin, Qian Mei, Jinxing Lv, and Chuan Wang. "Dual HER2 Blockade versus a Single Agent in Trastuzumab-Containing Regimens for HER2-Positive Early Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials." Journal of Oncology 2020 (March 16, 2020): 1–13. http://dx.doi.org/10.1155/2020/5169278.
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Purpose. Although trastuzumab is the standard of care for patients with human epidermal growth factor receptor 2 (HER2)- positive early breast cancer (EBC), drug resistance and disease relapse occur. Therefore, we performed a meta-analysis to assess the efficacy and safety of trastuzumab-containing dual anti-HER2 therapy compared to trastuzumab alone. Methods. A systematic search was performed to identify eligible randomized controlled trials (RCTs). Main outcomes including event-free survival/invasive disease-free survival (EFS/iDFS), overall survival (OS), and safety were considered. Results. Ten RCTs were included (15,284 patients). Significant improvements were observed in both EFS/iDFS (HR 0.86, p=0.0003) and OS (HR 0.86, p=0.02) with trastuzumab-based dual anti-HER2 therapy, especially in adjuvant treatment, while in the neoadjuvant setting, dual-targeted therapy also achieved a substantial pathological complete response (pCR) benefit (HR 1.34, p=0.0002). Subgroup analysis revealed that the EFS/iDFS benefit was slightly higher with trastuzumab plus pertuzumab or plus neratinib than trastuzumab plus lapatinib, while OS benefit was significant with trastuzumab plus lapatinib, but there were no subgroup differences (interaction test, p=0.80 and 0.24, resp.). In addition, EFS/iDFS benefit was unrelated to hormone receptor status but pronounced in the lymph node-positive (LN+) subgroup, which should be interpreted cautiously for lacking interaction (p=0.18). Besides, patients receiving dual therapy, especially with the lapatinib-containing regimen, experienced more toxicity, but no increase in cardiotoxicity. Conclusions. Despite being associated with more toxicity, trastuzumab-containing dual anti-HER2 therapy is superior to trastuzumab single agent for HER2-positive EBC independent of hormone receptor status. The correlation between survival and LN status needs further verification. Trastuzumab plus pertuzumab or plus neratinib is the preferred regimen with substantial efficacy and lower toxicity.
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Maddox, Adam L., Matthew S. Brehove, Kiarash R. Eliato, Andras Saftics, Eugenia Romano, Michael F. Press, Joanne Mortimer, et al. "Molecular Assessment of HER2 to Identify Signatures Associated with Therapy Response in HER2-Positive Breast Cancer." Cancers 14, no. 11 (June 4, 2022): 2795. http://dx.doi.org/10.3390/cancers14112795.
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Trastuzumab, the prototype HER2-directed therapy, has markedly improved survival for women with HER2-positive breast cancers. However, only 40–60% of women with HER2-positive breast cancers achieve a complete pathological response to chemotherapy combined with HER2-directed therapy. The current diagnostic assays have poor positive-predictive accuracy in identifying therapy-responsive breast cancers. Here, we deployed quantitative single molecule localization microscopy to assess the molecular features of HER2 in a therapy-responsive setting. Using fluorescently labeled trastuzumab as a probe, we first compared the molecular features of HER2 in trastuzumab-sensitive (BT-474 and SK-BR-3) and trastuzumab-resistant (BT-474R and JIMT-1) cultured cell lines. Trastuzumab-sensitive cells had significantly higher detected HER2 densities and clustering. We then evaluated HER2 in pre-treatment core biopsies from women with breast cancer undergoing neoadjuvant therapy. A complete pathological response was associated with a high detected HER2 density and significant HER2 clustering. These results established the nano-organization of HER2 as a potential signature of therapy-responsive disease.
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Iqbal, Muhammad Shahid, Ghazia Shaikh, Sanjoy Chatterjee, Helen Cocks, and Josef Kovarik. "Maintenance Therapy with Trastuzumab in Her2 Positive Metastatic Parotid Ductal Adenocarcinoma." Case Reports in Oncological Medicine 2014 (2014): 1–4. http://dx.doi.org/10.1155/2014/162534.
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Salivary ductal carcinomas (SDCs) are extremely rare and aggressive malignancies, accounting for approximately 6% of all salivary gland malignancies. One distinct feature is their resemblance to ductal carcinomas of breast. A significant percentage of SDCs overexpress Her2 and the use of targeted therapy with trastuzumab can be considered in these patients. We report a rare case of long term disease control with trastuzumab in Her2 positive metastatic parotid ductal carcinoma. Our case also highlights that isolated brain metastasis should be managed aggressively to allow optimal local control when systemic disease is under remission with trastuzumab. We have also reviewed the published literature on the use of trastuzumab in SDCs.
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Gutting, Tobias, Nadine Schulte, Sebastian Belle, Johannes Betge, Nicolai Härtel, Jürgen Wilke, Jürgen Weers, Matthias P. Ebert, and Tianzuo Zhan. "Complete Remission of Metastatic HER2+ Oesophagogastric Junctional Adenocarcinoma under long-term Trastuzumab Treatment." Journal of Gastrointestinal and Liver Diseases 28, no. 4 (December 9, 2019): 503–7. http://dx.doi.org/10.15403/jgld-397.
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Metastatic gastric cancer (GC) and oesophagogastric junctional (OGJ) adenocarcinoma have a poor clinical outcome with a high worldwide burden of disease. A 65-year old male patient with microcytic anemia was diagnosed with stage IV OGJ adenocarcinoma with multiple liver metastases. Immunohistochemical analysis revealed a high expression of HER2 (3+). Palliative chemotherapy with FLOT (oxaliplatin, 5-fluorouracil, leucovorin and docetaxel) in combination with trastuzumab was initiated. Due to severe adverse events, the therapy was de-escalated to trastuzumab monotherapy after six months of treatment. Initial restaging revealed partial response after the combination therapy of FLOT with trastuzumab. After reduction to trastuzumab monotherapy, the disease remained stable for two years until radiological complete response was observed. Trastuzumab monotherapy was continued for another two years to maintain complete response. Eleven months after the discontinuation of the therapy, no recurrence of the disease was detected. In conclusion, complete response can be achieved under trastuzumab monotherapy in exceptional responders.
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Joy, A. A., and J. R. Mackey. "The role of platinum-based therapy for HER-2-positive breast cancer." Breast Cancer Online 9, no. 4 (February 17, 2006): 1–7. http://dx.doi.org/10.1017/s1470903105004712.
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Trastuzumab is a monoclonal antibody targeting the human epidermal growth factor receptor-2 (HER-2) protein, the mediator of an aggressive breast cancer phenotype. Trastuzumab has an important role in the treatment of metastatic breast cancer (MBC) where it improves multiple endpoints, including overall survival. More recently, striking activity is also seen in non-MBC, with substantial benefits seen in both the neoadjuvant and adjuvant settings. Experimental data has identified synergistic therapeutic effects of platinum containing chemotherapeutic regimens when combined with trastuzumab. We review the pre-clinical and rapidly evolving clinical evidence supporting platinum and trastuzumab combinations for HER-2-positive breast cancer.
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Suvarna, S. K. "Cardiac pathology of fatal trastuzumab therapy." Journal of Clinical Pathology 61, no. 1 (September 14, 2007): 143–44. http://dx.doi.org/10.1136/jcp.2007.047464.
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Hortobagyi, Gabriel N. "Optimal duration of therapy with trastuzumab." Seminars in Oncology 28, no. 5N (October 2001): 33–40. http://dx.doi.org/10.1053/sonc.2001.28548.
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HORTOBAGYI, G. "Optimal duration of therapy with trastuzumab." Seminars in Oncology 28 (October 2001): 33–40. http://dx.doi.org/10.1016/s0093-7754(01)90280-5.
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Hua, Xin, Xi-Wen Bi, Jian-Li Zhao, Yan-Xia Shi, Ying Lin, Zhi-Yong Wu, Yuan-Qi Zhang, et al. "Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor–Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002)." Clinical Cancer Research 28, no. 4 (November 22, 2021): 637–45. http://dx.doi.org/10.1158/1078-0432.ccr-21-3435.
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Abstract Purpose: There is no research evidence demonstrate which is the better partner strategy, endocrine therapy or chemotherapy, to combine with anti-HER2 therapy as the first-line management of hormone receptor (HR)-positive (HR+) and HER2-positive (HER2+) metastatic breast cancer (MBC). We wished to ascertain if trastuzumab plus endocrine therapy is noninferior to trastuzumab plus chemotherapy. Patients and Methods: We conducted an open-label, noninferiority, phase III, randomized, controlled trial (NCT01950182) at nine hospitals in China. Participants, stratified by previous adjuvant endocrine therapy and disease status (recurrent disease vs. de novo metastasis), were assigned randomly (1:1) to receive trastuzumab plus endocrine therapy (per investigator's choice of oestrogen-receptor modulators or aromatase inhibitor, with/without concurrent ovarian suppression) or chemotherapy (per investigator's choice of taxanes, capecitabine, or vinorelbine). The primary endpoint was progression-free survival (PFS) with a noninferiority upper margin of 1.35 for the HR. The intention-to-treat population was used in primary and safety analyses. Results: A total of 392 patients were enrolled and assigned randomly to receive trastuzumab plus endocrine therapy (ET group, n = 196) or trastuzumab plus chemotherapy (CT group, n = 196). After a median follow-up of 30.2 months [interquartile range (IQR) 15.0–44.7], the median PFS was 19.2 months [95% confidence interval (CI), 16.7–21.7)] in the ET group and 14.8 months (12.8–16.8) in the CT group (hazard ratio, 0.88; 95% CI, 0.71–1.09; Pnoninferiority < 0.0001). A significantly higher prevalence of toxicity was observed in the CT group compared with the ET group. Conclusions: Trastuzumab plus endocrine therapy was noninferior to trastuzumab plus chemotherapy in patients with HR+HER2+ MBC.
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Yuan, Zhongyu, Jia-Jia Huang, Xin Hua, Jian-Li Zhao, Ying Lin, Yuan-Qi Zhang, Zhiyong Wu, et al. "Trastuzumab plus endocrine therapy or chemotherapy as first-line treatment for metastatic breast cancer with hormone receptor-positive and HER2-positive: The sysucc-002 randomized clinical trial." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 1003. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.1003.
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1003 Background: For metastatic breast cancer with hormone receptor-positive and HER2-positive, no evidence showed that which first-line regimens were preferred, either anti-HER2 therapy plus endocrine therapy or anti-HER2 therapy plus chemotherapy. This study aimed to determine whether trastuzumab plus endocrine therapy is as efficacious as trastuzumab plus chemotherapy and with decreased toxic effects. Methods: We conducted an open-label, non-inferiority, phase 3, randomized, controlled trial at nine hospitals in China. Patients with hormone receptor-positive and HER2-positive histologically confirmed advanced breast cancer were randomly assigned (1:1) to receive trastuzumab plus chemotherapy (CT group) or endocrine therapy (ET group). The primary endpoint was progression-free survival with a non-inferiority upper margin of 1.35 for the hazard ratio (HR). This trial is registered with ClinicalTrials.gov, number NCT01950182. Results: Between Sep 16, 2013, and Dec 28, 2019, 392 patients were enrolled and randomly assigned to receive trastuzumab plus endocrine therapy (n = 196) or trastuzumab plus chemotherapy (n = 196). In the intention-to-treat population, the median PFS was 14.8 months (95% CI 12.8-16.8) in the CT group and 19.2 months (95% CI 16.7-21.7) in the ET group (HR 0.88, 95% CI 0.71-1.09; Pnon-inferiority < 0.0001). Significantly higher frequency of toxicities were observed in CT group compared with ET group, including: leucopenia (98 [50%] vs 13 [6.6%]), nausea (93 [47%] vs 24 [12%]), fatigue (47 [24%] vs 31 [16%]), vomiting (45 [23%] vs 12 [6%]), headache (65 [33%] vs 24 [12%]) and alopecia (125 [64%] vs 8 [4%]). No patients died from treatment-related causes. Conclusions: Trastuzumab plus endocrine therapy was non-inferior to and had decreased toxicities to trastuzumab plus chemotherapy in patients with metastatic breast cancer with hormone receptor-positive and HER2-positive. Trastuzumab plus endocrine therapy could provide more convenient treatment and allow better treatment tolerance. Clinical trial information: NCT01950182 .
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Church, David N., and Chris G. A. Price. "A Review of Trastuzumab-Based Therapy in Patients with HER2-positive Metastatic Breast Cancer." Clinical Medicine. Therapeutics 1 (January 2009): CMT.S35. http://dx.doi.org/10.4137/cmt.s35.
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The ERBB2 or HER2 receptor is overexpressed in 25% of breast cancers and is associated with poor prognosis. Trastuzumab, a monoclonal antibody targeting HER2 has been demonstrated to improve survival when combined with chemotherapy for the treatment of HER2 overexpressing metastatic breast cancer (MBC). Further studies have endeavoured to clarify the optimum chemotherapy regimen in combination with trastuzumab for MBC and its use together with novel biological agents. This review summarises these data together with preclinical studies exploring the mechanism of trastuzumab action and causes of drug resistance. The frequent incidence of brain metastases in patients on trastuzumab is highlighted, and data on the continuation of trastuzumab following CNS and non-CNS progression reviewed.
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Jackson, Christopher, Leila Finikarides, and Alexandra L. J. Freeman. "The adverse effects of trastuzumab-containing regimes as a therapy in breast cancer: A piggy-back systematic review and meta-analysis." PLOS ONE 17, no. 12 (December 1, 2022): e0275321. http://dx.doi.org/10.1371/journal.pone.0275321.
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Background Trastuzumab is a valuable therapy option for women with ERBB2(HER2)+ breast cancer tumours, often used in combination with chemotherapy and alongside other therapies. It is known to have adverse effects, but these have proved difficult to separate from the effects of other concurrent therapies patients are usually taking. This study aims to assess the adverse effects specifically attributable to trastuzumab, and whether they vary by patient subgroup or concurrent therapies. Methods As registered on PROSPERO (CRD42019146541), we used previous systematic reviews as well as the clinicaltrials.gov registry to identify randomised controlled trials in breast cancer which compared treatment regimes with and without trastuzumab. Neoadjuvant, adjuvant and metastatic settings were examined. Data was extracted from those which had, as of July 2022, reported adverse events. Risk of bias was assessed using ROB2. Primary outcomes were adverse events of any type or severity (excluding death). A standard random-effects meta-analysis was performed for each outcome independently. In order to ascertain whether adverse effects differed by individual factors such as age or tumour characteristics, or by use of trastuzumab concurrently with hormone therapy, we examined individual-level patient data for one large trial, HERA. Results 79 relevant trials were found, of which 20 contained comparable arms of trastuzumab-containing therapy and corresponding matched therapy without trastuzumab. This allowed a comparison of 8669 patients receiving trastuzumab versus 9556 receiving no trastuzumab, which gave a list of 25 statistically and clinically significant adverse effects related to trastuzumab alone: unspecified pain, asthenia, nasopharyngitis, skin disorders (mainly rash), dyspepsia, paraesthesia, infections (often respiratory), increased lacrimation, diarrhoea, myalgia, oedema (limb/peripheral), fever, nose bleeds, cardiac events, insomnia, cough, back pain, dyspnoea, chills, dizziness or vertigo, hypertension, congestive heart failure, increased levels of aspartate aminotransferase, gastrointestinal issues and dehydration. Analysis of individual patient-level data from 5102 patients suggested that nausea is slightly more likely for women taking trastuzumab who are ER+ /also taking hormone therapy than for those who are ER-/not taking hormone therapy; no other potential treatment-subgroup interactions were detected. We found no evidence for significantly increased rates of neutropenia, anaemia or lymphopenia in patients on trastuzumab-containing regimes compared to those on comparable regimes without trastuzumab. Conclusions This meta-analysis should allow clinicians and patients to better identify and quantify the potential adverse effects of adding trastuzumab to their treatment regime for breast cancer, and hence inform their decision-making. However, limitations include serious risk of bias due to heterogeneity in reporting of the outcomes and the open-label nature of the trials.
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Hojan, Katarzyna, Karolina Gerreth, Danuta Procyk, Krystian Mania, Anna Zalewska, and Mateusz Maciejczyk. "Redox Status Response of Physical Exercise Training in Women with Breast Cancer during Trastuzumab Therapy." Healthcare 10, no. 10 (October 15, 2022): 2039. http://dx.doi.org/10.3390/healthcare10102039.
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Trastuzumab is indicated in the adjuvant setting for the early and intermediate stages of breast cancer (BC) positive for epidermal growth factor receptor 2 (HER2). Although HER2 in BC patients tends to disrupt pro-oxidant and inflammatory signaling, the influence of trastuzumab in modulating this process remains unknown. Due to the absence of any chemotherapeutic or chemoprophylactic agents for trastuzumab-induced side effects, this study investigated the potential role of regular physical exercise in modulating the antioxidant defenses, oxidative stress, and nitrosative damage in BC patients during trastuzumab treatment. Aim: The study aimed to analyze the relationship between regular physical activity and the redox status in women with BC during trastuzumab therapy. Materials and methods: We observed 50 BC patients during trastuzumab therapy in two groups: one that undertook moderately intensive supervised physical exercises, and a second that performed physical activity according to the recommendations for cancer patients, along with a third (control) group of healthy women. Results: The antioxidant enzyme and non-enzymatic antioxidant activities were significantly higher in the exercised group compared with the other participants. The concentrations of lipid and protein oxidative damage and nitrosative stress products were significantly higher in both BC groups than in the healthy controls. Conclusions: Trastuzumab treatment stimulates a redox response in BC patients. The results highlight the oxidative imbalance in parallel with regular physical training in women with BC during trastuzumab therapy. Further studies are needed to analyze different intensities and levels of physical training in women with BC during trastuzumab treatment.
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Hua, Jun, Zhe Zhang, Lili Zhang, Yan Sun, and Yuan Yuan. "UCP-2 inhibitor enhanced the efficacy of trastuzumab against HER2 positive breast cancer cells." Cancer Chemotherapy and Pharmacology 88, no. 4 (June 19, 2021): 633–42. http://dx.doi.org/10.1007/s00280-021-04303-4.
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Abstract Purpose This study aimed to investigate the possibility of UCP-2 inhibitor in reducing acquired resistance of trastuzumab to improve the outcome of patients receiving trastuzumab therapy by exploring the relationship between UCP-2 expression and HER2 signaling pathway and examining whether UCP-2 expression was modulated by trastuzumab treatment. Methods 32 women diagnosed with primary HER2-positive breast cancer were recruited in this study. Needle biopsy was obtained from patients before they received at least four cycles neoadjuvant therapy containing trastuzumab in combination with chemotherapy. Surgical tumor biopsy was obtained during surgical procedure after the neoadjuvant therapy. Levels of HER2 phosphorylation and UCP-2 expression were detected by immunohistochemistry (IHC) and compared between tumor needle biopsy tissue and surgical tumor samples of these patients, as well as in BT474 breast cancer cells before and after trastuzumab treatment. HER2-selective phosphorylation/kinase activity inhibitor ONT-380 was used to identify the correlation between HER2 phosphorylation level and UCP-2 expression. UCP-2 inhibitor Genipin was then used to evaluate the apoptosis index in BT474 cells treated with trastuzumab. Results UCP-2 expression was significantly elevated in surgical tumor samples from breast cancer patients receiving trastuzumab in a neoadjuvant setting. We further confirmed our findings in HER2-positive BT474 cell line and found that trastuzumab treatment induced phosphorylation of HER2 and the overexpression of UCP-2, and the latter can be reversed by HER2 selective kinase inhibitor ONT-380. Moreover, UCP-2 inhibitor Genipin significantly enhanced the proliferation suppression effects of trastuzumab and markedly promoted apoptosis. Conclusion Taken together, our study identified UCP-2 as a novel therapeutic target for HER2 positive breast cancer and UCP-2 inhibitor may have great potential to enhance the response rate and efficacy of trastuzumab therapy.
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Wang, Wei, Zhenhua Hu, Yu Huang, Huilin Zheng, Qiang Sun, Qifan Yang, Yuan Zhang, Linshi Zhang, and Weilin Wang. "Pretreatment with Gemcitabine/5-Fluorouracil Enhances the Cytotoxicity of Trastuzumab to HER2-Negative Human Gallbladder Cancer Cells In Vitro and In Vivo." BioMed Research International 2019 (March 25, 2019): 1–12. http://dx.doi.org/10.1155/2019/9205851.
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The effects of standard clinical therapies including surgery and chemotherapy are poor in advanced gallbladder cancer (GBC). There are a few reported cases of human epidermal growth factor receptor 2 (HER2)-positive GBC that responded well to trastuzumab. But trastuzumab has not yet been used to treat HER2-negative GBC. In this study, we investigated the cytotoxic effects of different combined therapies with trastuzumab and gemcitabine and/or 5-fluorouracil on HER2-negative GBC cell lines in vitro and in vivo. Trastuzumab alone showed almost no cytotoxicity to GBC cells with originally low HER2 gene amplification. Sequential therapy with chemotherapy followed by trastuzumab showed superiority over reverse sequential chemotherapy (P<0.05), concurrent combined chemotherapy (P<0.05), chemotherapy alone (P<0.05), and trastuzumab alone (P<0.05) in terms of cytotoxicity. Sequential therapy with chemotherapy followed by trastuzumab nearly completely inhibited cell viability in HER2-negative GBC cells. Similar results were observed with regard to apoptosis. Western blot analysis showed that gemcitabine/5-fluorouracil increased the expressions of total and phosphorylated forms of HER2, thus enhancing the cytotoxicity of trastuzumab. In vivo study verified the results of in vitro study by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay and immunohistochemical analysis. Moreover, not only the lightest tumor bearing but also the best survival state was detected in sequential therapy with chemotherapy followed by trastuzumab group compared with other groups. Our in vivo and in vitro data suggest that sequential therapy with gemcitabine/5-fluorouracil followed by trastuzumab represents a novel and promising therapeutic strategy against HER2-negative GBC. The upregulation of phosphorylated HER2 and phosphorylated-AKT induced by gemcitabine/5-fluorouracil treatment shows that HER2/AKT pathway is triggered.
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Mitri, Zahi, Tina Constantine, and Ruth O'Regan. "The HER2 Receptor in Breast Cancer: Pathophysiology, Clinical Use, and New Advances in Therapy." Chemotherapy Research and Practice 2012 (December 20, 2012): 1–7. http://dx.doi.org/10.1155/2012/743193.
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Human epidermal growth factor receptor 2 (HER2) is overexpressed in around 20–30% of breast cancer tumors. It is associated with a more aggressive disease, higher recurrence rate, and increased mortality. Trastuzumab is a HER2 receptor blocker that has become the standard of care for the treatment of HER2 positive breast cancer. The effectiveness of Trastuzumab has been well validated in research as well as in clinical practice. The addition of Trastuzumab to standard of care chemotherapy in clinical trials has been shown to improve outcomes for early stage as well as metastatic HER2 positive breast cancer. The most clinically significant side effect of Trastuzumab is the risk of cardiac myocyte injury, leading to the development of congestive heart failure. The emergence of patterns of resistance to Trastuzumab has led to the discovery of new monoclonal antibodies and other targeted agents aimed at overcoming Trastuzumab resistance and improving survival in patients diagnosed with HER2 positive breast cancers.
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Spector, Neil L., and Kimberly L. Blackwell. "Understanding the Mechanisms Behind Trastuzumab Therapy for Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer." Journal of Clinical Oncology 27, no. 34 (December 1, 2009): 5838–47. http://dx.doi.org/10.1200/jco.2009.22.1507.
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PurposeTargeted therapy with the humanized monoclonal antibody trastuzumab has become a mainstay for human epidermal growth factor receptor 2 (HER2) –positive breast cancer (BC). The mechanisms of action of trastuzumab have not been fully elucidated, and data available to date are reviewed here. The impact of the mechanisms of action on clinical benefit also is discussed.MethodsAn extensive literature review of trastuzumab and proposed mechanisms of action was performed.ResultsAt least five potential extracellular and intracellular antitumor mechanisms of trastuzumab have been identified in the preclinical setting. These include activation of antibody-dependent cellular cytotoxicity, inhibition of extracellular domain cleavage, abrogation of intracellular signaling, reduction of angiogenesis, and decreased DNA repair. These effects lead to tumor cell stasis and/or death. Clinical benefit from trastuzumab-based therapy in both early and advanced BC has been demonstrated. The benefit of trastuzumab use beyond progression has also been shown, which indicates the need for continuous suppression of the HER2 pathway. Targeting both HER2, with various approaches, and other pathways may enhance the clinical benefit observed with trastuzumab and overcome potential resistance. Novel combinations include pertuzumab (a HER2 dimerization inhibitor), lapatinib (a HER1/HER2 tyrosine kinase inhibitor), bevacizumab (an antiangiogenic agent), tanespimycin (a heat shock protein inhibitor), antiestrogen therapies, and an antibody-drug conjugate (trastuzumab-DM1).ConclusionTrastuzumab is the foundation of care for patients with HER2-positive BC. Emerging data from studies of other targeted agents may provide alternative treatment combinations to maximize the clinical benefit from trastuzumab and prevent or delay resistance. The continued development of trastuzumab highlights promising treatment approaches for the future.
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Blondeaux, Eva, Arlindo R. Ferreira, Francesca Poggio, Fabio Puglisi, Claudia Bighin, Federico Sottotetti, Filippo Montemurro, et al. "Clinical outcomes of patients with breast cancer relapsing after (neo)adjuvant trastuzumab and receiving trastuzumab rechallenge or lapatinib-based therapy: a multicentre retrospective cohort study." ESMO Open 5, no. 4 (August 2020): e000719. http://dx.doi.org/10.1136/esmoopen-2020-000719.
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BackgroundIn the prepertuzumab era, we evaluated the clinical outcomes of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who underwent first-line trastuzumab-based or lapatinib-based therapy according to prior exposure to (neo)adjuvant trastuzumab.Materials and methodsIn this multicentre retrospective cohort study conducted in 14 Italian centres of the Gruppo Italiano Mammella, consecutive patients undergoing first-line trastuzumab or lapatinib-based therapy were included. Analyses were performed according to the type of first-line therapy for metastatic disease (trastuzumab or lapatinib). Dichotomous clinical outcomes were analysed using logistic regression and time-to-event outcomes using Cox proportional hazard models controlling for relevant demographic, clinicopathological and therapy characteristics.ResultsOut of 450 patients included in the study, 416 (92%) received trastuzumab and 34 (7.5%) lapatinib. As compared with the trastuzumab cohort, more patients in the lapatinib cohort had a trastuzumab-free interval <1 month (37% vs 13.9%; p=0.017) and brain metastasis as first site of relapse (38.2% vs 9.4%; p<0.001). Among the 128 patients who relapsed after prior (neo)adjuvant trastuzumab, 101 (78.9%) received first-line trastuzumab and 27 (21.1%) first-line lapatinib. The following outcomes were observed with first-line lapatinib or trastuzumab, respectively: overall response rate 45.5% vs 61.3% (p=0.184), clinical benefit rate 68.2% vs 72.5% (p=0.691), median progression-free survival (PFS) 11.4 vs 12.0 months (p=0.814) and median overall survival (OS) 34.7 vs 48.2 months (p=0.722). In patients with brain metastasis as first site of relapse, median PFS was 12.2 vs 9.9 months (p=0.093) and median OS 33.7 vs 28.5 months (p=0.280), respectively.ConclusionsIn patients with HER2-positive breast cancer relapsing after prior (neo)adjuvant trastuzumab, first-line treatment with trastuzumab or lapatinib was not associated with a significant difference in the clinical outcomes. A non-significant trend favouring the use of lapatinib was observed in patients with brain metastasis as the first site of relapse.
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Chung, Clement, and Masha S. H. Lam. "Pertuzumab for the treatment of human epidermal growth factor receptor type 2-positive metastatic breast cancer." American Journal of Health-System Pharmacy 70, no. 18 (September 15, 2013): 1579–87. http://dx.doi.org/10.2146/ajhp120735.
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Abstract Purpose The pharmacology, pharmacokinetics, clinical efficacy, safety, and administration of pertuzumab in patients with metastatic human epidermal growth factor receptor type 2 (HER2)-positive breast cancer are reviewed. Summary Disease progression in HER2-positive breast cancer is often due to resistance to or a lack of efficacy of trastuzumab-based anti-HER2 therapy. Pertuzumab is the first humanized monoclonal antibody in a new class of drugs, the HER dimerization inhibitors, approved by the Food and Drug Administration for the first-line treatment of patients with metastatic HER2-positive breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. Since pertuzumab binds to a different epitope than trastuzumab, combination therapy with pertuzumab and trastuzumab results in a more complete blockade of HER2 signaling than trastuzumab monotherapy. The efficacy of adding pertuzumab to trastuzumab–docetaxel dual therapy was demonstrated in a pivotal randomized multicenter Phase III trial, which showed a significant benefit in terms of progression-free survival, with improved overall survival, in favor of the triple therapy as an initial regimen in treatment-naive patients with metastatic HER2-positive breast cancer. The combination of pertuzumab and trastuzumab has been found to have a tolerable toxicity profile. As clinical trials of pertuzumab for adjuvant, neoadjuvant, and metastatic-disease treatment continue, its role in the treatment of HER2-positive breast cancer will continue to evolve. Conclusion Pertuzumab, a novel HER2 dimerization inhibitor, has been shown to be effective in the treatment of metastatic HER2-positive breast cancer when used in combination with trastuzumab and docetaxel and is recommended for first-line therapy.
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Bloom, Meghan J., Patrick N. Song, John Virostko, Thomas E. Yankeelov, and Anna G. Sorace. "Quantifying the Effects of Combination Trastuzumab and Radiation Therapy in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer." Cancers 14, no. 17 (August 31, 2022): 4234. http://dx.doi.org/10.3390/cancers14174234.
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Background: Trastuzumab induces cell cycle arrest in HER2-overexpressing cells and demonstrates potential in radiosensitizing cancer cells. The purpose of this study is to quantify combination trastuzumab and radiotherapy to determine their synergy. Methods: In vitro, HER2+ cancer cells were treated with trastuzumab, radiation, or their combination, and imaged to evaluate treatment kinetics. In vivo, HER2+ tumor-bearing mice were treated with trastuzumab and radiation, and assessed longitudinally. An additional cohort was treated and sacrificed to quantify CD45, CD31, α-SMA, and hypoxia. Results: The interaction index revealed the additive effects of trastuzumab and radiation in vitro in HER2+ cell lines. Furthermore, the results revealed significant differences in tumor response when treated with radiation (p < 0.001); however, no difference was seen in the combination groups when trastuzumab was added to radiotherapy (p = 0.56). Histology revealed increases in CD45 staining in tumors receiving trastuzumab (p < 0.05), indicating potential increases in immune infiltration. Conclusions: The in vitro results showed the additive effect of combination trastuzumab and radiotherapy. The in vivo results showed the potential to achieve similar efficacy of radiotherapy with a reduced dose when combined with trastuzumab. If trastuzumab and low-dose radiotherapy induce greater tumor kill than a higher dose of radiotherapy, combination therapy can achieve a similar reduction in tumor burden.
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Lanning, Ryan Michael, Nadeem Riaz, Monica Morrow, Tracy-Ann Moo, Mahmoud El-Tamer, Kate Krause, Yu Chen, Xin Pei, Simon N. Powell, and Alice Y. Ho. "Effect of adjuvant trastuzumab on locoregional recurrence in human epidermal growth factor receptor 2-positive breast cancer treated with post-mastectomy radiation therapy." Journal of Clinical Oncology 31, no. 26_suppl (September 10, 2013): 61. http://dx.doi.org/10.1200/jco.2013.31.26_suppl.61.
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61 Background: HER2 overexpression is associated with an increased risk of LRR after mastectomy in the era prior to the use of adjuvant trastuzumab. The purpose of this study was to examine the effect of adjuvant trastuzumab on rates of LRR and whether this effect varied with the use of PMRT. Methods: From our institutional database, 474 women with Stage I-III HER2+ invasive breast cancer treated with mastectomy +/- adjuvant therapy from 1999-2007 were identified. Those patients lost to follow-up, treated with lapatinib, or diagnosed between 5/2004 to 5/2005 (when trastuzumab prescribing practices varied) were excluded; leaving 395 in the final study population. Two cohorts were compared: 139 women who received trastuzumab (5/2005-12/2007) and 256 women who did not (prior to 5/2005). Competing risks analyses were used to estimate cumulative incidence of LRR. Competing risks regression was used to evaluate the association between treatment factors and LRR. To minimize lead-time bias, patient data was censored at 5 years after mastectomy in both groups. Results: There were 18 LRRs in the entire cohort (16 no trastuzumab, 2 trastuzumab). Women in the no trastuzumab group were less likely to be node positive, receive chemotherapy or PMRT (all p<0.001). The hazard ratio for LRR was 0.218in the trastuzumab group (p= 0.04, 95% C.I. 0.05-0.94) with a 5-year risk of LRR of 1.5% in the trastuzumab versus 6.6% in the no trastuzumab group. After adjusting for PMRT and chemotherapy receipt, trastuzumab trended towards significance in decreasing LRR (p= 0.063). On subset analysis of 139 women who received PMRT, trastuzumab significantly reduced LRR (7.3% no trastuzumab, 0% trastuzumab, p=0.025). Among those who did not receive PMRT (256), trastuzumab did not significantly decrease LRR (6.3% no trastuzumab, 2.9 % trastuzumab, p=0.28). Conclusions: Adjuvant trastuzumab significantly reduced LRR in women with HER2+ breast cancer who received PMRT. A trend toward decreased LRR was observed in the entire population, but did not reach statistical significance, suggesting that the benefit is greater in HER2+ patients receiving multimodality therapy.
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File, Danielle, Giuseppe Curigliano, and Lisa A. Carey. "Escalating and De-escalating Therapy for Early-Stage HER2-Positive Breast Cancer." American Society of Clinical Oncology Educational Book, no. 40 (May 2020): 3–13. http://dx.doi.org/10.1200/edbk_100023.
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Untreated, HER2+ disease is the most aggressive breast cancer phenotype; however, the development of multiple highly effective HER2-targeting drugs has transformed treatment and survival. These drugs include the anti-HER2 monoclonal antibodies trastuzumab and pertuzumab; small molecule inhibitors lapatinib, neratinib, and tucatinib; and antibody-drug conjugates trastuzumab emtansine (T-DM1) and now trastuzumab deroxtecan. More complex regimens using these drugs continue to improve outcomes, but the incremental benefits of these advances are often modest. Improved outcomes came from the addition of HER2-targeted therapies to conventional chemotherapy, beginning with trastuzumab, then pertuzumab added to trastuzumab, or with neratinib given for the year after trastuzumab. Neoadjuvant, or preoperative, administration of chemotherapy plus HER2-targeting allows surgical deescalation and tailoring treatment by pathologic complete response (pCR) to therapy. Patients with pCR after conventional therapy have excellent outcomes; what we now know is that the poorer outcomes associated with residual disease can be ameliorated with adjuvant T-DM1. However, as we have developed more complex, effective, and expensive therapy to maximize outcomes, it is also true that we are overtreating many patients. In stage I HER2+ breast cancer, there are excellent outcomes with paclitaxel plus trastuzumab or T-DM1 alone. Higher clinical stage HER2+ disease is still treated aggressively, although intrinsic subtype or activated immune tumor microenvironment may identify those with augmented treatment response or better outcome. It is likely that future strategies to escalate and de-escalate treatment with less chemotherapy, fewer anti-HER2 drugs, or shorter duration will depend upon integrated clinical and genomic modeling.
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Ueno, Takayuki, Norikazu Masuda, Nobuaki Sato, Shoichiro Ohtani, Jun Yamamura, Nobuki Matsunami, Masahiro Kashiwaba, et al. "Multicenter study of primary systemic therapy with docetaxel, cyclophosphamide and trastuzumab for HER2-positive operable breast cancer: the JBCRG-10 study." Japanese Journal of Clinical Oncology 50, no. 1 (December 10, 2019): 3–11. http://dx.doi.org/10.1093/jjco/hyz119.
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Abstract Background The original aim of this study was to evaluate the treatment sequence and anthracycline requirement in docetaxel, cyclophosphamide and trastuzumab therapy. After one death in the anthracycline-containing arm, the protocol was amended to terminate the randomization. The single-docetaxel, cyclophosphamide and trastuzumab arm was continued to examine the efficacy and safety of the anthracycline-free regimen. Methods Women with human epidermal growth factor receptor-2-positive, operable and primary breast cancer were randomized to receive 5-fluorouracil, epirubicin and cyclophosphamide (four cycles) followed by docetaxel, cyclophosphamide and trastuzumab (four cycles), or docetaxel, cyclophosphamide and trastuzumab followed by 5-fluorouracil, epirubicin and cyclophosphamide, or docetaxel, cyclophosphamide and trastuzumab (six cycles). After the protocol amendment, patients were allocated to the docetaxel, cyclophosphamide and trastuzumab arm alone. The primary endpoint was a pathological complete response. Results In total, 103 patients were enrolled between September 2009 and September 2011: 21, 22 and 24 patients in the 5-fluorouracil, epirubicin and cyclophosphamide followed by docetaxel, cyclophosphamide and trastuzumab; docetaxel, cyclophosphamide and trastuzumab followed by 5-fluorouracil, epirubicin and cyclophosphamide and docetaxel, cyclophosphamide and trastuzumab arms, respectively, and 36 patients in the docetaxel, cyclophosphamide and trastuzumab arm after the protocol amendment. In total, 60 patients were allocated to the docetaxel, cyclophosphamide and trastuzumab arm, in which the pathological complete response rate was 45.8%, and disease-free survival at 3 years was 96.6%. Patients with stage I or IIA in the docetaxel, cyclophosphamide and trastuzumab arm showed good disease-free survival (100% at 3 years). The comparison of efficacy among the three arms was statistically underpowered. Left ventricular ejection fraction decreased significantly after 5-fluorouracil, epirubicin and cyclophosphamide followed by docetaxel–docetaxel, cyclophosphamide and trastuzumab (P = 0.017), but not after docetaxel, cyclophosphamide and trastuzumab followed by 5-fluorouracil, epirubicin and cyclophosphamide or docetaxel, cyclophosphamide and trastuzumab. Conclusions The pathological complete response rate for docetaxel, cyclophosphamide and trastuzumab was similar to previous reports of anthracycline-containing regimens. Docetaxel, cyclophosphamide and trastuzumab might be an option for primary systemic therapy in human epidermal growth factor receptor-2-positive early breast cancer. A larger confirmatory study is necessary.
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Mohammed, Samer Imad, Aya Thaer Sabry, and Dania Thaer Sabry. "Assessment of Health Beliefs Among Iraqi Breast Cancer Patients in Baghdad using either Tamoxifen or Trastuzumab." Iraqi Journal of Pharmaceutical Sciences ( P-ISSN: 1683 - 3597 , E-ISSN : 2521 - 3512) 30, no. 2 (December 11, 2021): 113–21. http://dx.doi.org/10.31351/vol30iss2pp113-121.
Full textAbstract:
Breast cancer is the most diagnosed form of malignant tumour in Iraqi women. Tamoxifen and trastuzumab are highly effective adjuvant therapy for breast cancer.
This study's objectives were to define the patient's belief in tamoxifen or trastuzumab when used as adjuvant therapy and to determine the variation in belief between the two medications in a sample of Iraqi breast cancer patients.
The cross-section survey was conducted using the BMQ-Specific questionnaire. Ninety-seven participants (sixty-seven tamoxifen, thirty trastuzumab) participated in this study.
The mean of specific-necessity scale for tamoxifen was (3.7) and for trastuzumab (4). The findings showed a high necessity for both medicines, and there were no significant differences in the scale of necessity between the two treatments. Regarding the scale of concern, the trastuzumab group's values are higher (3.35) than tamoxifen (3). Most participants who use tamoxifen or trastuzumab strongly agree with or agree with all the questions on the necessity scale with higher percentages for trastuzumab. Besides, the concern scale results showed the percentage of patients who agree / strongly agree is higher in the trastuzumab group. For the correlation between the need or concern score, the result showed only one significant negative correlation (R=-0.366, P-value=0.011) between the necessity score and the age of the participants for tamoxifen users. In Conclusion, this survey clearly showed a high level of necessity and a high level of concern regarding the use of two effective adjuvant therapy for women with breast cancer, tamoxifen and trastuzumab. Furthermore, this study shows that while the level of need for tamoxifen is higher than for trastuzumab, there were no significant variations between them.
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Hester, Anna, Paul Gaß, Peter A. Fasching, Anne Katrin Krämer, Johannes Ettl, Joachim Diessner, Achim Wöckel, et al. "Trastuzumab Biosimilars in the Therapy of Breast Cancer – “Real World” Experiences from four Bavarian University Breast Centres." Geburtshilfe und Frauenheilkunde 80, no. 09 (September 2020): 924–31. http://dx.doi.org/10.1055/a-1226-6666.
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Abstract Introduction With the introduction of the first trastuzumab biosimilar in the summer of 2018, biosimilar antibodies for breast cancer have found their way into the area of gynaecological oncology. The switch of anti-human epidermal growth factor receptor 2 (HER2) therapy from the reference drug Herceptin® to a biosimilar has presented challenges to the clinics. In addition to structural and organisational measures, training of employees as well as patient briefing and acceptance were major challenges. The study presented here records – within the context of quality assurance – how the switch to a trastuzumab biosimilar was implemented at four Bavarian university clinics in the Purchasing Association of Bavarian University Pharmacies. Materials/Methods Questionnaires on treatment figures and the switching process were sent to breast centres and pharmacies of four Bavarian university clinics between July and December 2019. The neoadjuvant, adjuvant and metastasised anti-HER2 therapy with trastuzumab with or without pertuzumab was recorded, evaluated and summarised. Results In the anti-HER2-therapy, trastuzumab was used intravenously (i. v.) and subcutaneously. Between July and December 2018, all four clinics in the Purchasing Association switched the i. v. trastuzumab therapy from the reference drug (Herceptin) to a biosimilar (for 2018: Kanjinti®). Over 200 patients were treated with trastuzumab i. v. in each of the two half-years of 2018 (before and after the switch). The spectrum of side effects and pCR rates under therapy with the biosimilar were comparable to the experiences made with the reference drug. Three out of four clinics provided training to employees and informed patients by means of a defined information leaflet. Patient acceptance was high. Summary The anti-HER2 therapy could be switched successfully and safely to trastuzumab biosimilars at the Bavarian university hospitals. This may serve as guideline for the further implementation of biosimilars. The structures necessary for this initial switching process have been prepared with trastuzumab as an example.
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Dorris, Kathleen, Melissa Widener, Vladimir Amani, Andrew Donson, Debra Schissel, Jessica Carson, Ashley Mettetal, et al. "EPCT-18. PHASE 0/I STUDY OF GM-CSF AND INTRATHECAL TRASTUZUMAB IN CHILDREN WITH RECURRENT POSTERIOR FOSSA EPENDYMOMA." Neuro-Oncology 22, Supplement_3 (December 1, 2020): iii307. http://dx.doi.org/10.1093/neuonc/noaa222.140.
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Abstract BACKGROUND Posterior fossa ependymoma (PF EPN) is a pediatric central nervous system malignancy that has a poor outcome to standard therapeutic approaches. The majority of PF EPN tumors have increased HER2 expression. Trastuzumab is a monoclonal antibody that targets HER2, and sargramostim (GM-CSF) stimulates hematopoietic progenitor cell proliferation. The combination of trastuzumab and GM-CSF has been shown to trigger antibody-dependent cell cytotoxicity in vitro in PF EPN cell lines. METHODS Children aged 1–21 years with relapsed PF EPN and no ventriculoperitoneal shunt or CSF obstruction are eligible for the Phase 0/I institutional trial at Children’s Hospital Colorado. Stratum 1 involves IT trastuzumab and subcutaneous (subQ) GM-CSF prior to standard-of-care surgical resection. Stratum 2 involves a 3 + 3 phase I design with serial IT trastuzumab doses, each preceded by three days of GM-CSF, to establish the MTD for IT trastuzumab. RESULTS Trastuzumab was detected in a sufficient number of tumors after presurgical IT delivery in Stratum 1 to open Stratum 2. Four patients (75% female) have been enrolled in Stratum 2 at trastuzumab Dose Level 1. Median age at enrollment is 9.8 years (range, 3.5–20.2 years). Preliminary CSF pharmacokinetic analysis demonstrated detectable trastuzumab up to 14 days after IT doses. No dose-limiting toxicities have occurred. Two patients progressed on therapy (median, 4 cycles). One patient is progression-free at 18 months off therapy. One patient remains on study therapy. CONCLUSIONS IT trastuzumab penetrates PF EPN tumor tissue. Stratum 2 remains open to accrual at Dose Level 2.
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Sasse, Andre Deeke, Flavio Mavignier Carcano, Lucas Vieira dos Santos, and Joao Paulo Da S. N. Lima. "Efficacy of different anti-HER2 drugs in first-line therapy for advanced breast cancer: Systematic review and meta-analysis." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): e11500-e11500. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.e11500.
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e11500 Background: Anti-HER2 therapy has brought major gains to therapy of advanced breast cancer (ABC), however it is still not know if there are difference in efficacy between trastuzumab and lapatinib. We execute a systematic review and meta-analysis in order to measure the impact of anti-HER2 therapy on ABC outcome and to assess if any particular drug is more effective in this scenario. Methods: Randomized controlled trials comparing first-line antineoplastic drug plus minus antiHER2 therapy (either trastuzumab or lapatinib) in ABC patients were searched in major meeting proceedings and databases. The outcomes were overall survival (OS), progression-free survival (PFS), tumor response and safety. Meta-analyses were performed using random-effects model and outcomes measured by hazard ratio (HR) and pertinent 95% confidence intervals were calculated. Subgroup analyses and meta-regression were undertaken to compare and measure the impact of anti-HER2 drug used over the estimated effect size. Results: eight trials (1848 patients) were included, two trials used lapatinib whereas six used trastuzumab. In two trials, anti-HER2 therapy was combined to hormone therapy. All trials, except the one by Slamon, demanded tumors to be ISH+ or IHC 3+. The methodological quality of included trials was moderate to good. Either trastuzumab or lapatinib improved overall survival (HR 0.79; 95% CI 0.69-0.91; P=0.0008; I2=0%) with no difference bet drugs (test for difference P=0.75). PFS was also increased with antiHER2 addition with similar activity of trastuzumab and lapatinib (HR = 0.58; 95% CI 0.51-0.66; P<0.0001; I2=0%, test for difference P= 0.42). Conclusions: The present meta-analysis confirmed the role of antiHER2 drugs as a valid first-line therapy for ABC. Furthermore, we failed to show any difference in efficacy between lapatinib and trastuzumab when combined to systemic therapy, both being acceptable options for antiHER2 therapy for ABC.
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Pal, S. K., A. Naeim, F. L. Wong, C. T. Chung, S. Bhatia, J. Mortimer, G. Somlo, S. Hurvitz, D. Villaluna, and A. Hurria. "Recommendation of adjuvant chemotherapy and trastuzumab in older adults with HER2-positive breast cancer: A survey of oncologists." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 9547. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.9547.
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9547 Background: Though substantial evidence supports the use of adjuvant trastuzumab in patients with HER2-positive breast cancer, a lesser amount of data is available to guide use of this therapy in older adults. The objective of the current study is to understand how patient age and health status impact the oncologists' decision to recommend adjuvant therapy in older women with HER2-positive breast cancer. Methods: Medical oncologists (n=151) participated in an online survey comprised of case scenarios with patients of varying age (70, 75, 80, 85) and health status (good, average, poor) with a T2(4 cm) N2(4+ LN) ER(-), HER2(+) breast cancer. Oncologists could offer the hypothetical patient treatment with chemotherapy and trastuzumab, chemotherapy alone, trastuzumab alone, or no therapy. The influence of age and health status on treatment recommendations was assessed using a generalized linear mixed-effects model. Results: With increasing age and deterioration of health status, the recommendation for chemotherapy with trastuzumab decreased (P<0.0001 for both). In contrast, recommendation for trastuzumab alone or no therapy increased with advancing age (P<0.0001 for both) and deteriorating health status (P<0.0035 and P=0.059, respectively). Chemotherapy alone was not frequently recommended, irrespective of age or health status. Conclusions: Given the relative dearth of evidence-based data for adjuvant treatment of HER2-positive breast cancer in older adults of varying health, oncologists recommend a diverse array of therapeutic approaches for this subgroup. Increasing age and declining health status lead to more frequent recommendation of trastuzumab alone or no therapy, and less frequent recommendation of chemotherapy with trastuzumab. [Table: see text] [Table: see text]
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OMAROVA, I. M., J. O. NURKETAEVA, and D. D. DOROGAN. "Calculation of the cost-effectiveness of subcutaneous administration of trastuzumab." Oncologia i radiologia Kazakhstana 55, no. 1 (March 31, 2020): 9–11. http://dx.doi.org/10.52532/2663-4864-2020-1-55-9-11.
Full textAbstract:
Rational selection of medicines with an assessment of their pharmacoeconomic effectiveness is the most effective way to
ensure safe and efficient treatment and economical use of budget funds allocated for drug therapy, as well as to reduce the
time of hospitalization and treatment of patients.
The purpose of the research was to evaluate the pharmacoeconomic effectiveness of using the subcutaneous and intravenous forms of drug Trastuzumab.
Research tasks:
1. Estimate costs when using subcutaneous trastuzumab in an outpatient chemotherapy room (OCR).
2. Estimate costs when using intravenous trastuzumab in a day patient department (DPD).
3. Estimate costs when using intravenous trastuzumab in a round-the-clock hospital.
Results: The paper presents the pharmacoeconomic analysis of targeted therapy with trastuzumab in two forms for intravenous administration (IV) and trastuzumab emtansine for subcutaneous administration (SC) in breast cancer by cost minimization method.
The costs of used drugs are according to the price-list of the unified national distributor SK Pharmacia as of January 1, 2018.
At comparable efficacy and toxicity, the estimated cost-effectiveness of trastuzumab per 100 patients per year is
KZT 16,939,600 ($ 50,972) for SC administration in OCR and IV administration in DPD vs. KZT 41,783,200 ($ 125,728) for
SC administration in OCR and IV administration in a round-the-clock hospital.
Conclusions: Based on the above, the subcutaneous form is economically feasible for conducting targeted therapy with
trastuzumab.
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Prempree, T., and C. Wongpaksa. "Mutations of HER2 gene in HER2-positive metastatic breast cancer." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 13118. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.13118.
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13118 Background: HER2 status of Breast Cancer has been assessed by IHC and FISH and used for therapeutic decision with a high degree of success. However, there were numbers of HER2-positive MBC who finally failed the Trastuzumab treatment after initial good response. Mechanisms of intrinsic and acquired Trastuzumab resistance are not yet known. Our Objective is to identify factor or factors responsible for Trastuzumab resistance. Methods: DNA extraction and Sequencing of HER2 gene were performed on primary tumors of HER2-positive 14 MBC patients undergoing Trastuzumab therapy. Re-biopsy were done on new metstatic sites of those cases discovered to have Trastuzumab resistance. Results: Of 14 MBC cases whose tumors showing positive IHC and FISH, there were no mutation found in their HER2 gene, exons 18,19, 20 and 21. However, 3 of 14 cases of MBC undergoing continuous Trastuzumab therapy with excellent response for more than one year, developed the resistance. All three cases had new metstatic sites biopsied, and showed D880N and E837Y mutations in the exon 21 of their HER2 genes. All three cases showed no response to trastuzumab therapy. Conclusions: 1) HER2-positive MBC tumors did not have any HER2 gene mutations in them. 2) Mutations arised in their HER2 gene, exon 21 may be responsible for the intrinsic and acquired Trastuzumab resistance. Additional work in this area is needed to further substantiate our findings. No significant financial relationships to disclose.
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Marinko, Tanja, Jure Dolenc, and Cvetka Bilban-Jakopin. "Cardiotoxicity of concomitant radiotherapy and trastuzumab for early breast cancer." Radiology and Oncology 48, no. 2 (June 1, 2014): 105–12. http://dx.doi.org/10.2478/raon-2013-0040.
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AbstractBackground. Trastuzumab therapy given in combination with one of several chemotherapy regimens is currently considered the standard of care for the treatment of early-stage, human epidermal growth factor receptor-2 (HER2) -positive breast cancer. The treatment with trastuzumab is due to a significant impact on the survival part of the standard adjuvant treatment of patients with HER2-positive breast cancer. Patients treated with postoperative breast or chest wall irradiation receive trastuzumab concomitant with radiotherapy. In a small proportion of patients trastuzumab causes cardiotoxicity. Preclinical findings indicate a radiosensibilizing effect of trastuzumab in breast cancer cells, but it is not yet clear whether it radiosensibilizes cells of healthy tissues too.Conclusions. Special attention is required when left breast or left thoracic wall is irradiated in patient receiving trastuzumab, because long-term effects of the concurrent treatment with trastuzumab and radiotherapy are not yet known. In an era where more patients are surviving a diagnosis of breast cancer, better understanding and earlier detection of therapy-induced cardiac toxicity will be of paramount importance.
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Acevedo-Gadea, Carlos, Christos Hatzis, Gina Chung, Neal Fishbach, Kimberly Lezon-Geyda, Daniel Zelterman, Michael P. DiGiovanna, Lyndsay Harris, and Maysa M. Abu-Khalaf. "Sirolimus and trastuzumab combination therapy for HER2-positive metastatic breast cancer after progression on prior trastuzumab therapy." Breast Cancer Research and Treatment 150, no. 1 (February 2015): 157–67. http://dx.doi.org/10.1007/s10549-015-3292-8.
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