Gyawali B, et al. – An analysis was performed to gauge the duration of adjuvant trastuzumab in HER2 positive breast cancer. As compared to shorter durations, one year of trastuzumab prolonged overall, and disease–free survivals in women with early-stage HER2 positive breast cancer, and this should remain as the standard of care. With the 1–year treatment, cardiotoxicity increased significantly.

Methods

• In order to determine Randomized Controlled Trials (RCTs) comparing one year versus shorter durations of trastuzumab in adjuvant treatment of breast cancer, Medline, Embase, and major conference proceedings were searched systematically in June 2017.
• By using generic inverse-variance, reported Hazard-Ratios (HR) for Overall Survival (OS) and Disease-Free Survival (DFS), and Odds-Ratio for cardiac events, with respective 95% Confidence Intervals (CI) from each study was weighted, and pooled in a meta-analysis.
• This study employed I2, and chi2 statistics to appraise inter-study heterogeneity and sub-group difference (based on hormone-receptors and node-positivity).

Results

• Inclusion criteria were met by four studies (n=7614).
• Moreover, individual RCTs had diverse pre-specified upper-limits of 95% CI for declaring non-inferiority (range: <1.15 to <1.53).
• As compared to shorter durations, pooled results demonstrated significant improvements in OS (HR 1.28, p=0.04), and DFS (HR 1.24, p=0.005) with 1 year of trastuzumab.
• Despite non-inferiority designs of individual trials, absence of multiplicity argument allowed for declaring superiority of 1 year of trastuzumab based on the results.
• There was no influence on overall effect by duration of trastuzumab in experimental arm (9 weeks versus 6 months).
• This study did not find statistical interaction by hormone-receptor status and node-positivity on overall results [p(sub-group difference) 0.73, and 0.52, respectively].
• In addition, odds-Ratio for cardiac events was 2.65 (p<0.001) favoring shorter duration.