Neal E Ready1, Patrick A Ott2, Matthew D Hellmann3, Jon Zugazagoitia4, Christine L Hann5, Filippo de Braud6, Scott J Antonia7, Paolo A Ascierto8, Victor Moreno9, Akin Atmaca10, Stefania Salvagni11, Matthew Taylor12, Asim Amin13, D Ross Camidge14, Leora Horn15, Emiliano Calvo16, Ang Li17, Wen Hong Lin17, Margaret K Callahan18, David R Spigel19. 1. Duke University Medical Center, Durham, North Carolina. Electronic address: neal.ready@duke.edu. 2. Dana Farber Cancer Institute, Boston, Massachusetts. 3. Memorial Sloan-Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York. 4. University Hospital 12 de Octubre, Madrid, Spain. 5. Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. 6. Fondazione IRCCS Istituto Nazionale dei Tumori, Milan; University of Milan, Milan, Italy. 7. H. Lee Moffitt Cancer Center, Tampa, Florida. 8. Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale", Naples, Italy. 9. START Madrid - FJD, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain. 10. Department of Oncology and Hematology, Krankenhaus Nordwest, UCT-University Cancer Center, Frankfurt, Germany. 11. Policlinico S.Orsola-Malpighi, Azienda Ospedaliero Universitaria, Bologna, Italy. 12. Oregon Health & Science University, Portland, Oregon. 13. Levine Cancer Institute, Atrium Healthcare System, Charlotte, North Carolina. 14. University of Colorado Denver, Aurora, Colorado. 15. Vanderbilt Ingram Cancer Center, Nashville, Tennessee. 16. START Madrid - CIOCC, Centro Integral Oncológico Clara Campal, Madrid, Spain. 17. Bristol-Myers Squibb, Lawrenceville, New Jersey. 18. Memorial Sloan-Kettering Cancer Center, New York, New York. 19. Sarah Cannon Research Institute/Tennessee Oncology Nashville, Nashville, Tennessee.
Abstract
INTRODUCTION: Nivolumab monotherapy is approved in the United States for third-line or later metastatic small cell lung cancer based on pooled data from nonrandomized and randomized cohorts of the multicenter, open-label, phase 1/2 trial of nivolumab ± ipilimumab (CheckMate 032; NCT01928394). We report updated results, including long-term overall survival (OS), from the randomized cohort. METHODS: Patients with small cell lung cancer and disease progression after one to two prior chemotherapy regimens were randomized 3:2 to nivolumab 3 mg/kg every 2 weeks or nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks for four cycles followed by nivolumab 3 mg/kg every 2 weeks. Patients were stratified by number of prior chemotherapy regimens and treated until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by blinded independent central review. RESULTS: Overall, 147 patients received nivolumab and 96 nivolumab plus ipilimumab. Minimum follow-up for ORR/progression-free survival/safety was 11.9 months (nivolumab) and 11.2 months (nivolumab plus ipilimumab). ORR increased with nivolumab plus ipilimumab (21.9% versus 11.6% with nivolumab; odds ratio: 2.12; 95% confidence interval: 1.06-4.26; p = 0.03). For long-term OS, minimum follow-up was 29.0 months (nivolumab) versus 28.4 months (nivolumab plus ipilimumab); median (95% confidence interval) OS was 5.7 (3.8-7.6) versus 4.7 months (3.1-8.3). Twenty-four-month OS rates were 17.9% (nivolumab) and 16.9% (nivolumab plus ipilimumab). Grade 3 to 4 treatment-related adverse event rates were 12.9% (nivolumab) versus 37.5% (nivolumab plus ipilimumab), and treatment-related deaths were n =1 versus n = 3, respectively. CONCLUSIONS: Whereas ORR (primary endpoint) was higher with nivolumab plus ipilimumab versus nivolumab, OS was similar between groups. In each group, OS remained encouraging with long-term follow-up. Toxicities were more common with combination therapy versus nivolumab monotherapy.
INTRODUCTION: Nivolumab monotherapy is approved in the United States for third-line or later metastatic small cell lung cancer based on pooled data from nonrandomized and randomized cohorts of the multicenter, open-label, phase 1/2 trial of nivolumab ± ipilimumab (CheckMate 032; NCT01928394). We report updated results, including long-term overall survival (OS), from the randomized cohort. METHODS: Patients with small cell lung cancer and disease progression after one to two prior chemotherapy regimens were randomized 3:2 to nivolumab 3 mg/kg every 2 weeks or nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks for four cycles followed by nivolumab 3 mg/kg every 2 weeks. Patients were stratified by number of prior chemotherapy regimens and treated until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by blinded independent central review. RESULTS: Overall, 147 patients received nivolumab and 96 nivolumab plus ipilimumab. Minimum follow-up for ORR/progression-free survival/safety was 11.9 months (nivolumab) and 11.2 months (nivolumab plus ipilimumab). ORR increased with nivolumab plus ipilimumab (21.9% versus 11.6% with nivolumab; odds ratio: 2.12; 95% confidence interval: 1.06-4.26; p = 0.03). For long-term OS, minimum follow-up was 29.0 months (nivolumab) versus 28.4 months (nivolumab plus ipilimumab); median (95% confidence interval) OS was 5.7 (3.8-7.6) versus 4.7 months (3.1-8.3). Twenty-four-month OS rates were 17.9% (nivolumab) and 16.9% (nivolumab plus ipilimumab). Grade 3 to 4 treatment-related adverse event rates were 12.9% (nivolumab) versus 37.5% (nivolumab plus ipilimumab), and treatment-related deaths were n =1 versus n = 3, respectively. CONCLUSIONS: Whereas ORR (primary endpoint) was higher with nivolumab plus ipilimumab versus nivolumab, OS was similar between groups. In each group, OS remained encouraging with long-term follow-up. Toxicities were more common with combination therapy versus nivolumab monotherapy.
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