Suresh S Ramalingam1, Silvia Novello2, Salih Zeki Guclu3,4, Dmitry Bentsion5, Zanete Zvirbule6, Maria Szilasi7, Reyes Bernabe8, Konstantinos Syrigos9, Lauren Averett Byers10, Philip Clingan11, Jair Bar12, Everett E Vokes13, Ramaswamy Govindan14, Martin Dunbar15, Peter Ansell15, Lei He15, Xin Huang15, Vasudha Sehgal15, Jaimee Glasgow15, Bruce A Bach15, Julien Mazieres16. 1. Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA. 2. Department of Oncology, University of Turin, AOU San Luigi Gonzaga, Orbassano, Torino, Italy. 3. Chest Diseases Clinic, Izmir Chest Diseases Research Hospital, Izmir, Turkey. 4. Current affiliation: Ozel Gazi Hospital, Izmir, Turkey. 5. Sverdlovsk Regional Oncology Center, Yekaterinburg, Russia. 6. Riga Eastern Clinical University Hospital, Latvian Oncology Center, Riga, Latvia. 7. Department for Pulmonology, University of Debrecen, Debrecen, Hungary. 8. Hospital Universitario Virgen del Rocio, Seville, Spain. 9. 3rd Department of Medicine, National & Kapodistrian University of Athens, Greece. 10. Department of Thoracic and Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX. 11. Southern Medical Day Care Centre, Wollongong, NSW, Australia. 12. Institute of Oncology, Sheba Medical Center, Tel HaShomer, Ramat Gan, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 13. University of Chicago, Chicago, IL. 14. Washington University, St Louis, MO. 15. AbbVie Inc, North Chicago, IL. 16. Toulouse University Hospital, Institut Universitaire du Cancer, Université Paul Sabatier, Toulouse, France.
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 (n = 486) or placebo (n = 484); 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 = .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 = 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.
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 (n = 486) or placebo (n = 484); 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 = .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 = 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.
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