Comparison of Sequential and Concomitant Adjuvant Trastuzumab Treatment in HER2+ Breast Cancer

Adjuvant clinical trials in early human epidermal growth factor receptor 2–positive (HER2+) breast cancer have generally only assessed sequential or concomitant incorporation of trastuzumab with chemotherapy. Only a single trial, NCCTG-N9831, has prospectively compared the 2 modalities head-to-head, and although the results did not show a statistically significant difference between them, the authors of that study concluded that, based on the trend of a positive risk–benefit ratio, the concurrent treatment with taxane should be the recommended modality. In this study, using the SIGNAL and PHARE cohorts, investigators compared the efficacy of concomitant versus sequential adjuvant treatment with trastuzumab.

The SIGNAL study (RECF1098) was a prospective genome-wide association study, and PHARE was a randomized phase 3 clinical trial (NCT00381901) designed to evaluate trastuzumab efficacy in women with nonmetastatic breast cancer. The comparison in the HER2+ group of adjuvant trastuzumab and chemotherapy modalities was based on a propensity score methodology applying the inverse probability of treatment weighting method in the Cox regression model. “This methodology might allow one to obtain unbiased estimates of average treatment effects in retrospective analysis,” said Dr Marco Colleoni of Milan, Italy, who was unaffiliated with the study. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method, and comparisons between groups were based on the log-rank test.

The SIGNAL/PHARE cohort included 11,728 breast cancer cases, with 5502 being HER2+ tumors. Of these, 1897 (34.5%) were treated by sequential and 3605 (65.5%) were treated by concomitant administration of taxane-chemotherapy and trastuzumab. The adjusted comparison found similar OS between the 2 groups (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.86-1.19). DFS was also similar between the 2 administration modalities (HR, 1.08; 95% CI, 0.96-1.21).

These results suggest that, counter to previous recommendations, the sequential administration of trastuzumab given after the completion of adjuvant chemotherapy might be as valid as the concomitant administration of trastuzumab and taxane chemotherapy in the adjuvant setting. “We can therefore save time for the patient by using concomitant rather than sequential administration,” said Dr Xavier Pivot of Besancon, France, who was an author on the study.

Pivot X, et al. ESMO 2016. Abstract 144O.