Abstract P6-14-05: Final Overall Survival Analysis of the TBP Phase III Study (GBG 26/BIG 3-05): Capecitabine vs. Capecitabine + Trastuzumab in Patients with HER2-Positive Metastatic Breast Cancer Progressing during Trastuzumab Treatment

Background: In women with HER2-positive breast cancer progressing during trastuzumab treatment, continuation of trastuzumab plus capecitabine (XH) showed a significantly improved overall response rate and time to progression compared with capecitabine (X) alone (von Minckwitz et al, J Clin Oncol 27:1999-2006, 2009). Here we report the final analysis of overall survival (OS). Methods: Patients (pts) with HER2-positive, locally advanced or metastatic breast cancer who progressed during treatment with trastuzumab with or without adjuvant and/or 1 st -line metastatic chemotherapy were prospectively randomized to X (2500 mg/m2 on days 1-14, q3w) or XH (6 mg/kg, q3w). OS was a pre-specified secondary endpoint of the study. Results: Median follow up at June 2010 was 20.7 months. 59 of 74 and 60 of 77 pts died in the X alone and XH arm, respectively. Median OS was 20.6 and 24.9 months with X alone and XH, respectively. This difference was not statistically significant (HR=0.94 [0.65-1.35]; p=0.73). Cox proportional hazard model showed performance status, hormone receptor status and metastatic site as independent prognosticators for survival. No difference between treatment arms was observed for pts with a clinical response or clinical benefit, respectively. Pts who continued/restarted anti-HER2 treatment (trastuzumab or lapatinib) after 2 nd progression (N=88) had an OS of 18.8 compared with 13.3 months for those who did not receive 3 rd line treatment with anti-HER2 agents (N=52) (HR 0.63; p=0.02). Pts who continued treatment after progression as initially randomized (anti-HER2 treatment after XH (N=31) or no anti-HER2 treatment after X alone (N=53)) had an OS of 26.7 months and 20.4 months (HR 0.71; p=0.2). Conclusions: Final OS analysis of the GBG-26 study could not demonstrate a survival benefit for treatment beyond progression with trastuzumab. However in a post-hoc analysis, pts receiving anti-HER2 treatment as 3 rd line therapy showed a better OS than those not receiving this targeted treatment. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-14-05.