Global phase III study of gemcitabine plus paclitaxel (GT) vs. paclitaxel (T) as frontline therapy for metastatic breast cancer (MBC): First report of overall surviva

Abstract

510 Background: GT had phase II safety and efficacy in MBC after anthracyclines, so it was compared to T in a phase III study of frontline therapy. Accrual goals were met in 4/02 and at initial planned interim analysis, GT significantly improved time to progression (TTP), progression-free survival (PFS), objective response rates (ORR) and quality of life, with an acceptable toxicity profile (PASCO 22:161, 2003). It was uncertain if this would translate into overall survival (OS) benefit, the primary endpoint of the trial. This report presents the first OS analysis. Methods: Patients (pts) with measurable MBC, prior (neo)adjuvant anthracyclines and KPS ≥70 were randomized to GT (G 1250 mg/m2 d1,8; T 175 mg/m2 d1) or T (175 mg/m2 d1) q21 days to progression. With median follow-up of 15.6 mos (all but 1 pt off study), the first OS analyses by Kaplan-Meier and Cox regression were conducted at approximately 75% (343) of the deaths needed (440) for the planned final OS report. (All p-values are 2-sided; confidence intervals, 95%.) Results: Characteristics of the 529 eligible pts (267 GT, 262 T) with visceral-dominant disease; toxicity; and the significant benefit from GT in ORR, TTP and PFS were previously reported (ref. above). 38% on GT stopped therapy due to progression vs 55% on T; therapy ended due to adverse events in 6.7%, GT vs 5.0%, T. The OS hazard ratio (HR) was 0.775 (.627, .959) in favor of GT, p=.018. Median OS for GT was 18.5 mos (16.5–21.2) vs T, 15.8 mos (14.4–17.4). One-year survival was 70.7% (65.1–76.3%) for GT and 60.9% (54.8–66.9%) for T (p=.019). The HR in favor of GT persisted in Cox regression after adjusting for baseline covariates: 0.740 (.598, .915), p=.006. Second-line therapy was nearly identical between arms, except for a 4-fold greater use of gemcitabine in the T arm. Conclusions: GT provides significant OS advantage over T when both are given on a q3 week cycle, a result to be confirmed in the final planned analysis in late 2004. The TTP benefit predicted OS improvement with longer follow-up. GT should be considered a frontline regimen in MBC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Eli Lilly Eli Lilly