Background: One year of adjuvant trastuzumab, chosen empirically, improves survival of women with early-stage, Human Epidermal Growth Factor Receptor 2 (HER2) positive breast cancer. Two years of trastuzumab does not improve efficacy but increases cost, inconvenience, and adverse effects. We aimed to evaluate if less than 1 year of adjuvant trastuzumab retained efficacy while reducing toxicities and cost.
Methods: We performed a pooled analyses of efficacy and toxicity from Randomized Controlled Trials (RCTs) comparing 1 year of trastuzumab to shorter durations in adjuvant treatment of HER2-positive breast cancer. Hazard Ratios (HR) for Overall Survival (OS) and Disease-Free Survival (DFS), and Odds Ratios (OR) for cardiac events with respective 95% Confidence Intervals (CI) were weighted using generic inverse variance approach and pooled in meta-analyses using random effects models with RevMan 5.3 software. Sub-group analyses of outcomes based on Estrogen Receptor (ER) and nodal status were performed.
Results: Five RCTs involving approximately 12,000 patients qualified-three assessing 6 months and two assessing 9 weeks of trastuzumab compared to 1 year. All RCTs were designed to test non-inferiority of the shorter treatment. One year of trastuzumab resulted into better OS (pooled HR 1.23, 95% CI 1.07-1.42) and DFS (pooled HR 1.21, 95% CI 1.09-1.36) in overall population, but the benefit of longer treatment was statistically insignificant in node negative (HR 1. 20, p = 0.11), and ER positive disease (HR 1.15, p = 0.09). Odds ratio for cardiac events was significantly higher with the longer duration (OR 2.48, p < 0.001).
Conclusion: One year of trastuzumab for adjuvant treatment of breast cancer improves outcomes compared to shorter treatments in overall population. Cardiotoxicity is increased with the longer treatment.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s10549-018-4967-8 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Impact of adjuvant trastuzumab therapy and its discontinuation on cardiac function and mortality in patients with early-stage breast cancer: An analysis based on the Japanese Receipt Claim Database.
Breast
December 2024
Department of Clinical Research and Management, Graduate School of Medicine, University of Ryukyus, Japan; Department of Clinical Pharmacology, Faculty of Medicine, University of the Ryukyus, Japan. Electronic address:
Standard trastuzumab therapy can reduce the risk of early recurrence of HER2-positive breast cancer. However, trastuzumab-induced cardiac dysfunction may force the discontinuation of adjuvant trastuzumab therapy. Incidentally, there are still unclear whether or not trastuzumab treatment should be continued in the setting of reduced cardiac function.
View Article and Find Full Text PDFImmune regulatory adjuvant approach to mitigate subcutaneous immunogenicity of monoclonal antibodies.
Front Immunol
December 2024
Department of Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, United States.
Introduction: Immunogenicity continues to be a challenge for development and clinical utility of monoclonal antibodies, and there are gaps in our current ability to prevent anti-drug antibody development in a safe and antigen-specific manner.
Methods: To mitigate immunogenicity of monoclonal antibodies administered subcutaneously, O-phospho-L-serine (OPLS)-the head group of the tolerance-inducing phospholipid, phosphatidylserine-was investigated as an immunoregulatory adjuvant.
Results: Formulations of adalimumab, trastuzumab or rituximab with OPLS showed reduction in relative immunogenicity in mice compared to vehicle formulations, indicated by reduced anti-drug antibody development and significant reductions in CD138+ plasma cell differentiation in bone marrow.
Prognostic value of residual disease (RD) biology and gene expression changes during the neoadjuvant treatment in patients with HER2+ early breast cancer (EBC).
Ann Oncol
December 2024
Lineberger Comprehensive Center, University of North Carolina, Chapel Hill, NC, USA; Division of Hematology-Oncology, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address:
Background: In HER2+ early breast cancer (EBC), we investigated tumor and immune changes during neoadjuvant treatment and their impact on residual disease (RD) biology and prognostic implications across 4 neoadjuvant studies of trastuzumab with or without lapatinib, and with or without chemotherapy: CALGB 40601, PAMELA, NeoALTTO and NSABP B-41.
Patients And Methods: We compared tumor and immune gene expression changes during neoadjuvant treatment and their association with with event-free survival (EFS) by uni- and multivariable Cox regression models in different cohorts and timepoints: 452 RD samples at baseline including 169 with a paired RD, and biomarker changes during neoadjuvant therapy, evaluating model performance via the c-index.
Results: Analysis of 169 paired tumor samples revealed a shift in intrinsic subtype proportions from HER2-Enriched at baseline (50.
Tolerability and Preliminary Outcomes of Adjuvant T-DM1 in HER2-Positive Breast Cancer After Neoadjuvant Therapy: The ATD Study.
Cancers (Basel)
December 2024
Phase IV Clinical Studies Unit, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy.
Background/objectives: HER2-positive breast cancer (HER2BC) is an aggressive subtype, with neoadjuvant treatment (NAT) aiming to achieve a pathological complete response (pCR) to improve long-term outcomes. Trastuzumab emtansine (T-DM1) has been established as the standard of care in the adjuvant setting for HER2BC patients who do not obtain pCR. The ATD study aimed to evaluate the real-world tolerability of T-DM1 in this setting.
View Article and Find Full Text PDFFibroblast growth factor receptor four inhibitor FGF401 improves the efficacy of trastuzumab in FGFR4-overexpressing breast cancer cells.
Int J Cancer
December 2024
Department of Biological Science & Technology, College of Life Sciences, China Medical University, Taichung, Taiwan.
Breast cancer is the most common cancer among women. Among them, human epidermal growth factor receptor-positive (HER2+) breast cancer is more malignant. Fortunately, many anti-HER2 drugs are currently used in clinical treatments to increase patient survival.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!