Optimal duration of adjuvant trastuzumab in treatment of early breast cancer: a meta-analysis of randomized controlled trials
- 459 Downloads
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.
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.
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).
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.
KeywordsBreast cancer Herceptin Duration Adjuvant
Compliance with ethical standards
Conflict of interest
Institutional research grant from Pfizer (SN). Neither of the authors have personal conflict of interest.
- 3.Earl HM, Hiller L, Vallier A-L et al (2018) PERSEPHONE: 6 versus 12 months (m) of adjuvant trastuzumab in patients (pts) with HER2 positive (+) early breast cancer (EBC): randomised phase 3 non-inferiority trial with definitive 4-year (yr) disease-free survival (DFS) results. J Clin Oncol 36:506CrossRefGoogle Scholar
- 8.Mavroudis D, Saloustros E, Malamos N et al (2015) Six versus 12 months of adjuvant trastuzumab in combination with dose-dense chemotherapy for women with HER2-positive breast cancer: a multicenter randomized study by the Hellenic Oncology Research Group (HORG). Ann Oncol 26(7):1333–1340Google Scholar
- 10.Joensuu H, Fraser J, Wildiers H et al. (2018) Effect of adjuvant trastuzumab for a duration of 9 weeks vs 1 year with concomitant chemotherapy for early human epidermal growth factor receptor 2-positive breast cancer: the SOLD Randomized Clinical Trial. JAMA OncolGoogle Scholar