Veliparib in Combination with Carboplatin and Etoposide in Patients with Treatment-Naïve Extensive-Stage Small Cell Lung Cancer: A Phase 2 Randomized Study.

Purpose This study investigated the efficacy and safety of oral PARP inhibitor veliparib, plus carboplatin and etoposide in patients with treatment-naive extensive-stage small cell lung cancer (ED-SCLC). Experimental design Patients were randomized 1:1:1 to veliparib (240 mg twice daily [BID] for 14 days) plus chemotherapy followed by veliparib maintenance (400 mg BID; veliparib throughout), veliparib plus chemotherapy followed by placebo (veliparib combination only), or placebo plus chemotherapy followed by placebo (control). Patients received 4-6 cycles of combination therapy, then maintenance until unacceptable toxicity/progression. The primary endpoint was progression-free survival (PFS) with veliparib throughout versus control. Results Overall (N=181), PFS was improved with veliparib throughout versus control (hazard ratio [HR] 0.67 [80% confidence interval (CI): 0.50-0.88], P=0.059); median PFS was 5.8 and 5.6 months, respectively. There was a trend towards improved PFS with veliparib throughout versus control in SLFN11-positive patients (HR 0.6; 80% CI: 0.36-0.97). Median overall survival (OS) was 10.1 versus 12.4 months in the veliparib throughout and control arms, respectively (HR 1.43, 80% CI: 1.09-1.88). Grade 3/4 adverse events were experienced by 82%, 88%, and 68% of patients in the veliparib throughout, combination only, and control arms, most commonly hematologic. Conclusions Veliparib plus platinum chemotherapy followed by veliparib maintenance demonstrated improved PFS as first-line treatment for ED-SCLC with an acceptable safety profile, but there was no corresponding benefit in OS. Further investigation is warranted to define the role of biomarkers in this setting.