Veliparib Plus Carboplatin and Paclitaxel Versus Investigator's Choice of Standard Chemotherapy in Patients With Advanced Non–Squamous Non–Small Cell Lung Cancer

•Veliparib + chemotherapy (CT) did not improve OS versus CT alone in unselected NSCLC.•In the unselected population, median OS was 12.1 months in both treatment arms.•In LP52+ patients, median OS was 11.2 versus 9.2 months (HR 0.644; P = .113).•LP52 signature may be used to identify patients with poor prognosis.•LP52+ patients are more likely to benefit from the addition of veliparib to CT. This open-label Phase III trial (NCT02264990) evaluated the PARP inhibitor, veliparib, combined with carboplatin/paclitaxel versus chemotherapy alone for first-line treatment of patients with advanced non–squamous non–small cell lung cancers (NSCLC). A 52-gene expression classifier (LP52) previously shown to identify patients more likely to respond to veliparib was evaluated as a planned correlative analysis. Adult current or former smokers with advanced non–squamous NSCLC were randomized 1:1 to veliparib (120 mg daily for 7 days/cycle) with carboplatin and paclitaxel or to investigators’ choice of platinum doublet chemotherapy (up to 6, 21-day cycles), with optional pemetrexed maintenance. Prospective analysis of the LP52 signature was conducted using a clinical Qiagen/HTG assay. The primary endpoint was overall survival (OS) in LP52+ patients. Overall, 595 patients received veliparib + carboplatin/paclitaxel (n = 298) or chemotherapy alone (n = 297); 13% (n = 40) in each arm were LP52+. The primary endpoint was not met; median OS was 11.2 months with veliparib + carboplatin/paclitaxel versus 9.2 months with chemotherapy alone in the LP52+ subgroup (hazard ratio [HR] 0.644, 95% confidence interval [CI]: 0.396-1.048; P = .113). In the overall population, median OS was 12.1 months in both arms (HR 0.986, 95% CI: 0.827-1.176; P = .846). No new safety signals were observed. In patients with non–squamous NSCLC, there was no significant improvement in OS with veliparib + carboplatin/paclitaxel versus chemotherapy alone, although a trend toward improved OS in the LP52+ population suggests this subgroup may benefit from veliparib. Statistical power was limited due to the small sample size. Patients with advanced non–squamous non–small cell lung cancers without oncogenic drivers have poor treatment outcomes. Overall, no survival benefit was observed in patients (N = 595) receiving veliparib plus chemotherapy versus chemotherapy alone. However, in the LP52+ population (n = 80), patients receiving veliparib plus chemotherapy trended toward improved survival. The LP52 signature ma