A randomized phase III study of iniparib (BSI-201) in combination with gemcitabine/carboplatin (G/C) in metastatic triple-negative breast cancer (TNBC).

Abstract

1007 Background: A randomized phase II study in mTNBC suggested that iniparib (I), an anticancer agent with PARP inhibitory activity, added to GC improved overall survival (OS), without potentiating GC toxicity (O’Shaughnessy et al. NEJM 2011). This confirmatory study evaluated the safety and efficacy of GC with or without I in a similar mTNBC pt population. Methods: This randomized, open-label phase III study enrolled pts ≥18 years with mTNBC, measurable disease, and ≤2 prior cytotoxic regimens for metastatic TNBC. Pts were stratified based on having 0 vs. 1–2 prior metastatic therapies. Pts were randomized (1:1) to GC alone or GCI. G (1000 mg/m2; IV) and C (AUC 2; IV) were given on days 1 and 8, and I (5.6 mg/kg; IV) on days 1, 4, 8, and 11 every 21 days. Upon central confirmation of disease progression on GC, crossover to GCI was permitted. Primary endpoints were OS and progression-free survival (PFS); secondary endpoints were objective response rate and safety. Results: Between July 2009 and March 2010, 519 pts were randomized. Pt characteristics were balanced between the two arms. The study did not meet the criteria for significance for co-primary endpoints of OS and PFS. Efficacy results in pts stratified by line of therapy (57% in 1st line; 43% in 2nd or 3rd line) will be presented. 152 of 258 GC pts (59%) crossed over to receive GCI following disease progression. Most frequently occurring grade 3/4 adverse events included neutropenia (53% [GC] vs. 61% [GCI]), anemia (22% vs. 18%), thrombocytopenia (24% vs. 28%), and leukopenia (15% vs. 16%). Overall, addition of I did not significantly add to the toxicity profile of GC alone. Conclusions: Although this study demonstrated a consistent safety profile to that of the phase II study, addition of I to GC did not meet the pre-specified criteria for significance for co-primary endpoints of OS and PFS in pts with mTNBC. Analyses aimed at further elucidating these findings are ongoing (clinicaltrials.gov: NCT00938652). GC (n = 258 ) GCI (n = 261) Hazard ratio (95% CI) P value* Median OS, months 11.1 11.8 0.876 (0.687−1.116) 0.284 Median PFS, months 4.1 5.1 0.794 (0.646−0.976) 0.027 * Based on 2-sided log-rank test.