Short-duration versus 1-year adjuvant trastuzumab in early HER2 positive breast cancer: A meta-analysis of randomized controlled trials

Abstract

Background: One year of adjuvant trastuzumab treatment is the standard of care for early stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients; however, controversy remains regarding the optimal schedule of trastuzumab because the selection of the 1-year schedule was arbitrary. After the remarkable results of the PERSEPHONE trial as well as the updated final results of the PHARE trial, we performed an updated meta-analysis to reassess the efficacy and safety of shorter durations of trastuzumab.

Methods: A literature search of databases was conducted to identify randomized controlled trials reporting the efficacy and cardiotoxicity of shorter-duration and standard 1-year trastuzumab treatment. The hazard ratios (HRs) of disease-free survival (DFS) and overall survival (OS), and the odds ratios (ORs) of cardiac events were also estimated and pooled.

Results: Six studies were eligible, including a total of 11,496 patients. Both DFS (HR = 1.13; 95% confidence interval [CI] = 1.03-1.25; p = 0.01) and OS (HR = 1.16; 95% CI = 1.01-1.32; p = 0.03) were significantly improved with conventional 1-year trastuzumab treatment compared with shorter treatments. The more pronounced survival benefits observed in patients with negative estrogen receptor (ER) tumor and nodal involvement should be interpreted cautiously because of the lack of interaction between the survival benefit and ER, as well as the nodal status (interaction test, ER status: p = 0.26; nodal status: p = 0.60). One year of trastuzumab treatment resulted in a substantial DFS benefit compared with shorter schedules when administered concurrently with chemotherapy (HR = 1.22; 95% CI = 1.09-1.38; p = 0.0008; p = 0.02 for the interaction test). Patients in the shorter duration group experienced significantly fewer cardiac events (OR = 0.52; 95% CI = 0.43-0.62; p < 0.00001).

Conclusions: Though correlated with an increasing risk of cardiotoxicity, 1 year of adjuvant trastuzumab treatment conferred substantial survival benefits and should remain as the preferred treatment for early stage HER2-positive breast cancer. Shorter durations of trastuzumab may serve as an alternative choice for patients with cardiac disease and those at lower risk of recurrence.

Keywords: Adjuvant treatment; Breast cancer; HER2; Short-duration; Trastuzumab.