Joyce O'Shaughnessy, MD
The addition of the PARP inhibitor iniparib failed to improve overall survival (OS) or progression-free survival (PFS) when added to gemcitabine/carboplatin (GC) compared with GC alone in patients with metastatic triple-negative breast cancer (TNBC). TNBC lacks estrogen receptors, progesterone receptors, and HER2 receptors—the most common targets for breast cancer treatments. Results of this randomized phase III study (BSI-201) were disappointing because a previous phase II trial suggested that iniparib plus GC was highly effective in this patient population.
Perhaps the explanation for the difference between the phase II and III studies lies in the heterogeneity of the TNBC population, suggested lead author Joyce O'Shaughnessy, MD, a medical oncologist at Baylor Charles A. Sammons Cancer Center in Dallas, Texas.
TNBC is biologically heterogeneous and can be classified as claudin-low, basal-like HER2-enriched, luminal A, and luminal B. To explore the possibility that heterogeneity within TNBC affected study results, the authors are analyzing molecular subtyping of specimens from 304 patients with regard to response to iniparib.
The randomized, open-label, phase III trial enrolled 519 patients treated with GC alone or GC plus iniparib (GCI). Cycles were given every 21 days until disease progression, and then patients in the GC arm were allowed to cross over to GCI (59% of patients did so). Baseline characteristics were well-balanced. About 57% received study therapy as first-line and 43% received it second-line; 30% received prior bevacizumab.
The median disease-free interval was 15 months for GC and 12 months for GCI. Prior to crossover, no major differences were seen between the 2 treatment arms for neutropenia, thrombocytopenia, and anemia. Deaths were uncommon; 1 treatment-related death was reported in the GCI arm.
Table. Efficacy Endpoints in the Intent-to-Treat Population
N = 258
N = 261
HR (95% CI)
Median PFS, mo
Median OS, mo
GC indicates gemcitabine/carboplatin; GCI, gemcitabine/carboplatin plus iniparib; m, months; PFS, progression-free survival; OS, overall survival.
Adapted from from O'Shaughnessy et al. J Clin Oncol. 2011;29(suppl; abstr 1007).
PFS was 4.1 months for GC versus 5.1 months for GCI (hazard ratio [HR] = 0.079; P
= .027). Median OS was 11.1 months versus 11.8 months, respectively (HR = 0.88; P
= .284). Overall response rate was 30% versus 34%, respectively. No difference in PFS or OS was observed for either arm when patients were receiving first-line therapy. For those treated with secondor third-line therapy, an exploratory analysis suggested a possible benefit for the addition of iniparib (PFS, HR = 0.67; OS, HR = 0.65).