Trastuzumab beyond progression for HER2 positive metastatic breast cancer: progression-free survival on first-line therapy predicts overall survival impact.

Trastuzumab beyond first progression in the metastatic setting has been adopted based on limited data suggesting improved outcomes compared to second-line chemotherapy alone although predictive factors for preferential benefit remain elusive. We conducted a retrospective review of all patients receiving trastuzumab for HER2 + metastatic disease between Jan 1, 1999-June 15, 2011. Univariate and time to event analyses described treatment and survival patterns. Median duration of each line of therapy and overall survival times for covariates, including treatment era (pre versus post Jan 1, 2005), lines of trastuzumab-based therapy (1 versus 2 versus 3 + ), first-line chemotherapy partner (docetaxel/paclitaxel versus other) and median exposure to first-line trastuzumab-based therapy (=/> versus < cohort median) were estimated. A total of 119 patients received a median of two lines of trastuzumab-based therapy (range 1-8). Median overall survival was 21.8 months (95% CI = 14.5-27.1 m), by era was 15.6 m (95% CI = 9.7-24.8 m) versus 26.1 m (95% CI = 20.0-39.3 m; p = 0.11) and by lines of trastuzumab-based therapy received was 10.6 m (95% CI = 5.3-17.4 m) versus 13.9 m (95% CI = 9.5-27.6 m) versus 32.5 m (95% CI = 25-49.4 m) (p = 0.0014). Median overall survival was significantly longer for those receiving taxanes with trastuzumab compared to other first line partners (26.1 m, 95% CI = 17.8-31.4 m versus 14.5 m, 95% CI = 9.4-21.9 m, p = 0.02). Median overall survival with duration of first-line trastuzumab-based therapy =/> cohort median was 31.9 m (95% CI = 26.2-52.2 m) versus 10.3 m for shorter durations (95% CI = 6.9-15.6 m; p < 0.0001). Our observations support progression-free survival on first-line trastuzumab-based therapy as a clinically relevant predictive factor for overall survival benefit with the adoption of a trastuzumab beyond progression treatment strategy.