D R Spigel1, D Vicente2, T E Ciuleanu3, S Gettinger4, S Peters5, L Horn6, C Audigier-Valette7, N Pardo Aranda8, O Juan-Vidal9, Y Cheng10, H Zhang11, M Shi12, A Luft13, J Wolf14, S Antonia15, K Nakagawa16, J Fairchild17, C Baudelet18, D Pandya19, P Doshi20, H Chang21, M Reck22. 1. Oncology Department, Sarah Cannon Research Institute/Tennessee Oncology, PLLC, Nashville, USA. Electronic address: David.spigel@sarahcannon.com. 2. Department of Medical Oncology, Hosp Univ Virgen Macarena, Seville, Spain. 3. Medical Oncology, Prof. Dr. Ion Chiricuta Institute of Oncology and UMF Iuliu Hatieganu, Cluj-Napoca, Romania. 4. Medical Oncology, Yale Cancer Center, New Haven, USA. 5. Oncology Department, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland. 6. Department of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, USA. 7. Pulmonology Department, Hôpital Sainte Musse, Toulon, France. 8. Thoracic Unit, Medical Oncology Department, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (VHIO), Barcelona. 9. Department of Medical Oncology, Hospital Universitario La Fe, Valencia, Spain. 10. Department of Thoracic Oncology, Jilin Cancer Hospital, Changchun, Jilin, China. 11. Department of Oncology, Tangdu Hospital, Xi'an, Shaanxi, China. 12. Department of Medical Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China. 13. Department of Thoracic Surgery, Leningrad Regional Clinical Hospital, St. Petersburg, Russian Federation. 14. Clinic I for Internal Medicine, Center for Integrated Oncology, University Hospital of Cologne, Cologne, Germany. 15. Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA. 16. Department of Medical Oncology, Kindai University Hospital, Osaka, Japan. 17. Clinical Development, Bristol Myers Squibb, Princeton, USA. 18. Global Drug Development, Biometrics & Data Sciences, Bristol Myers Squibb, Princeton, USA. 19. Translational Pathology, Bristol Myers Squibb, Princeton, USA. 20. Translational Medicine, Bristol Myers Squibb, Princeton, USA. 21. Translational Bioinformatics, Bristol Myers Squibb, Princeton, USA. 22. Thoracic Oncology, LungenClinic Grosshansdorf, Airway Research Center North, German Center of Lung Research, Grosshansdorf, Germany.
Abstract
BACKGROUND: Patients with relapsed small-cell lung cancer (SCLC) have few treatment options and dismal survival. Phase I/II data show activity of nivolumab in previously treated SCLC. PATIENTS AND METHODS: CheckMate 331 is a randomized, open-label, phase III trial of nivolumab versus standard chemotherapy in relapsed SCLC. Patients with relapse after first-line, platinum-based chemotherapy were randomized 1 : 1 to nivolumab 240 mg every 2 weeks or chemotherapy (topotecan or amrubicin) until progression or unacceptable toxicity. Primary endpoint was overall survival (OS). RESULTS: Overall, 284 patients were randomized to nivolumab and 285 to chemotherapy. Minimum follow-up was 15.8 months. No significant improvement in OS was seen with nivolumab versus chemotherapy [median OS, 7.5 versus 8.4 months; hazard ratio (HR), 0.86; 95% confidence interval (CI), 0.72-1.04; P = 0.11]. A survival benefit with nivolumab was suggested in patients with baseline lactate dehydrogenase ≤ upper limit of normal and in those without baseline liver metastases. OS (nivolumab versus chemotherapy) was similar in patients with programmed death-ligand 1 combined positive score ≥1% versus <1%. Median progression-free survival was 1.4 versus 3.8 months (HR, 1.41; 95% CI, 1.18-1.69). Objective response rate was 13.7% versus 16.5% (odds ratio, 0.80; 95% CI, 0.50-1.27); median duration of response was 8.3 versus 4.5 months. Rates of grade 3 or 4 treatment-related adverse events were 13.8% versus 73.2%. CONCLUSION: Nivolumab did not improve survival versus chemotherapy in relapsed SCLC. No new safety signals were seen. In exploratory analyses, select baseline characteristics were associated with improved OS for nivolumab.
BACKGROUND: Patients with relapsed small-cell lung cancer (SCLC) have few treatment options and dismal survival. Phase I/II data show activity of nivolumab in previously treated SCLC. PATIENTS AND METHODS: CheckMate 331 is a randomized, open-label, phase III trial of nivolumab versus standard chemotherapy in relapsed SCLC. Patients with relapse after first-line, platinum-based chemotherapy were randomized 1 : 1 to nivolumab 240 mg every 2 weeks or chemotherapy (topotecan or amrubicin) until progression or unacceptable toxicity. Primary endpoint was overall survival (OS). RESULTS: Overall, 284 patients were randomized to nivolumab and 285 to chemotherapy. Minimum follow-up was 15.8 months. No significant improvement in OS was seen with nivolumab versus chemotherapy [median OS, 7.5 versus 8.4 months; hazard ratio (HR), 0.86; 95% confidence interval (CI), 0.72-1.04; P = 0.11]. A survival benefit with nivolumab was suggested in patients with baseline lactate dehydrogenase ≤ upper limit of normal and in those without baseline liver metastases. OS (nivolumab versus chemotherapy) was similar in patients with programmed death-ligand 1 combined positive score ≥1% versus <1%. Median progression-free survival was 1.4 versus 3.8 months (HR, 1.41; 95% CI, 1.18-1.69). Objective response rate was 13.7% versus 16.5% (odds ratio, 0.80; 95% CI, 0.50-1.27); median duration of response was 8.3 versus 4.5 months. Rates of grade 3 or 4 treatment-related adverse events were 13.8% versus 73.2%. CONCLUSION: Nivolumab did not improve survival versus chemotherapy in relapsed SCLC. No new safety signals were seen. In exploratory analyses, select baseline characteristics were associated with improved OS for nivolumab.
Authors: Evelyn M Nguyen; Hirokazu Taniguchi; Joseph M Chan; Yingqian A Zhan; Xiaoping Chen; Juan Qiu; Elisa de Stanchina; Viola Allaj; Nisargbhai S Shah; Fathema Uddin; Parvathy Manoj; Michael Liu; Sheng F Cai; Ross Levine; Álvaro Quintanal-Villalonga; Triparna Sen; Andrew Chow; Charles M Rudin Journal: J Thorac Oncol Date: 2022-06-09 Impact factor: 20.121
Authors: A-M C Dingemans; M Früh; A Ardizzoni; B Besse; C Faivre-Finn; L E Hendriks; S Lantuejoul; S Peters; N Reguart; C M Rudin; D De Ruysscher; P E Van Schil; J Vansteenkiste; M Reck Journal: Ann Oncol Date: 2021-04-20 Impact factor: 51.769