Veliparib in Combination With Platinum-Based Chemotherapy for First-Line Treatment of Advanced Squamous Cell Lung Cancer: A Randomized, Multicenter Phase III Study

• Type of Material: Article
• Authors: Suresh Ramalingam, Emory University; Silvia Novello, University of Turin; Salih Zeki Guclu, Izmir Chest Diseases Research Hospital; Dmitry Bentsion, Sverdlovsk Regional Oncology Center; Zanete Zvirbule, Riga Eastern Clinical University Hospital; Maria Szilasi, University of Debrecen; Reyes Bernabe, Hospital Universitario Virgen del Rocio; Konstantinos Syrigos, National & Kapodistrian University of Athens; Lauren Averett Byers, University of Texas MD Anderson Cancer Center; Philip Clingan, Southern Medical Day Care Centre; Jair Bar, Sheba Medical Center; Everett E Vokes, University of Chicago; Ramaswamy Govindan, Washington University; Martin Dunbar, AbbVie Inc; Peter Ansell, AbbVie Inc; Lei He, AbbVie Inc; Xin Huang, AbbVie Inc; Vasuha Sehgal, AbbVie Inc; Jaimee Glasgow, AbbVie Inc; Bruce A Bach, AbbVie Inc; Julien Mazieres, Université Paul Sabatier
• Language: English
• Date: 2021-11-10
• Publisher: LIPPINCOTT WILLIAMS & WILKINS
• Publication Version: Final Published Version
• Copyright Statement: © 2021 by American Society of Clinical Oncology
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1200/JCO.20.03318
• Title of Journal or Parent Work: JOURNAL OF CLINICAL ONCOLOGY
• Volume: 39
• Issue: 32
• Start Page: 3633
• End Page: +
• Keywords: NIVOLUMAB; FEATURES; CARCINOMA; Oncology; RISK; SMOKING; GENE-EXPRESSION; PARP INHIBITOR VELIPARIB; Science & Technology; DAMAGE; Life Sciences & Biomedicine
• Research Categories: Health Sciences, Oncology

Abstract

PURPOSE Squamous non-small-cell lung cancer (sqNSCLC) is genetically complex with evidence of DNA damage. This phase III study investigated the efficacy and safety of poly (ADP-ribose) polymerase inhibitor veliparib in combination with conventional chemotherapy for advanced sqNSCLC (NCT02106546). PATIENTS AND METHODS Patients age $ 18 years with untreated, advanced sqNSCLC were randomly assigned 1:1 to carboplatin and paclitaxel with veliparib 120 mg twice daily (twice a day) or placebo twice a day for up to six cycles. The primary end point was overall survival (OS) in the veliparib arm versus the control arm in current smokers, based on phase II findings. Archival tumor samples were provided for biomarker analysis using a 52- gene expression histology classifier (LP52). RESULTS Overall, 970 patients were randomly assigned to carboplatin and paclitaxel plus either veliparib (n5486) or placebo (n5484); 57% were current smokers. There was no significant OS benefit with veliparib in current smokers, with median OS 11.9 versus 11.1 months (hazard ratio [HR], 0.905; 95% CI, 0.744 to 1.101; P 5 .266). In the overall population, OS favored veliparib; median OS was 12.2 versus 11.2 months (HR, 0.853; 95% CI, 0.747 to 0.974), with no difference in progression-free survival (median 5.6 months per arm). In patients with biomarker-evaluable tumor samples (n 5 360), OS favored veliparib in the LP52-positive population (median 14.0 v 9.6 months; HR, 0.66; 95% CI, 0.49 to 0.89), but favored placebo in the LP52-negative population (median 11.0 v 14.4 months; HR, 1.33; 95% CI, 0.95 to 1.86). No new safety signals were observed in the experimental arm. CONCLUSION In current smokers with advanced sqNSCLC, there was no therapeutic benefit of adding veliparib to first-line chemotherapy. The LP52 signature may identify a subgroup of patients likely to derive benefit from veliparib with chemotherapy.