Randomized, Placebo-Controlled, Phase II Study of Veliparib in Combination with Carboplatin and Paclitaxel for Advanced/Metastatic Non-Small Cell Lung Cancer

Purpose: Poly(ADP-ribose) polymerase (PARP) plays a critical role in DNA repair. Veliparib, a PARP inhibitor, enhances the efficacy of platinum-based chemotherapies and has been safely combined with carboplatin and paclitaxel. This phase II trial aimed to evaluate whether the addition of veliparib to carboplatin and paclitaxel improves progression-free survival (PFS) in treatment-naïve patients with advanced or metastatic non-small cell lung cancer (NSCLC).
Experimental Design: Patients were randomized in a 2:1 ratio to receive carboplatin and paclitaxel combined with either veliparib or placebo. Veliparib (120 mg) or placebo was administered on days 1 through 7 of each 3-week cycle, while carboplatin (AUC = 6 mg/mL/min) and paclitaxel (200 mg/m²) were given on day 3, for up to six cycles.
Results: A total of 158 patients were enrolled (median age: 63 years; 68% male; 48% with squamous histology). Median PFS was 5.8 months in the veliparib group versus 4.2 months in the placebo group (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.45–1.15; P = 0.17). Median overall survival (OS) was 11.7 months in the veliparib arm compared to 9.1 months in the ABT-888 placebo arm (HR, 0.80; 95% CI, 0.54–1.18; P = 0.27). Among patients with squamous histology, trends favored veliparib for both PFS (HR, 0.54; 95% CI, 0.26–1.12; P = 0.098) and OS (HR, 0.73; 95% CI, 0.43–1.24; P = 0.24). The objective response rate was comparable between groups (32.4% for veliparib vs. 32.1% for placebo), but the duration of response favored veliparib (HR, 0.47; 95% CI, 0.16–1.42; P = 0.18). Rates of grade III/IV neutropenia, thrombocytopenia, and anemia were similar across both arms.
Conclusions: The combination of veliparib with carboplatin and paclitaxel was well-tolerated and demonstrated favorable trends in PFS and OS compared to chemotherapy alone, particularly in patients with squamous histology, who exhibited the most benefit.