Michael Boyer1, Mehmet A N Şendur2, Delvys Rodríguez-Abreu3, Keunchil Park4, Dae Ho Lee5, Irfan Çiçin6, Perran Fulden Yumuk7, Francisco J Orlandi8, Ticiana A Leal9, Olivier Molinier10, Nopadol Soparattanapaisarn11, Adrian Langleben12, Raffaele Califano13, Balazs Medgyasszay14, Te-Chun Hsia15, Gregory A Otterson16, Lu Xu17, Bilal Piperdi17, Ayman Samkari17, Martin Reck18. 1. Chris O'Brien Lifehouse, Camperdown, NSW, Australia. 2. Ankara Yıldırım Beyazıt University, Faculty of Medicine and Ankara City Hospital, Ankara, Turkey. 3. Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain. 4. Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. 5. Asan Medical Center, Seoul, South Korea. 6. Trakya University, Erdine, Turkey. 7. Marmara University School of Medicine, Istanbul, Turkey. 8. Orlandi-Oncología, Providencia, Chile. 9. University of Wisconsin Carbone Cancer Center, Madison, WI. 10. Hospital of Le Mans, Le Mans, France. 11. Mahidol University, Sriraj Hospital, Bangkok, Thailand. 12. St. Mary's Hospital - ODIM, McGill University Department of Oncology, Montreal, QC, Canada. 13. The Christie NHS Foundation Trust, and Division of Cancer Sciences, The University of Manchester, Manchester, UK. 14. Veszprém Megyei Tüdőgyógyintézet Farkasgyepű, Farkasgyepű, Hungary. 15. China Medical University and China Medical University Hospital, Taichung, Taiwan. 16. The Ohio State University-James Comprehensive Cancer Center, Columbus, OH. 17. Merck & Co, Inc, Kenilworth, NJ. 18. LungenClinic, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany.
Abstract
PURPOSE:Pembrolizumab monotherapy is standard first-line therapy for metastatic non-small-cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1) tumor proportion score (TPS) ≥ 50% without actionable driver mutations. It is not known whether adding ipilimumab to pembrolizumab improves efficacy over pembrolizumab alone in this population. METHODS: In the randomized, double-blind, phase III KEYNOTE-598 trial (ClinicalTrials.gov identifier: NCT03302234), eligible patients with previously untreated metastatic NSCLC with PD-L1 TPS ≥ 50% and no sensitizing EGFR or ALK aberrations were randomly allocated 1:1 to ipilimumab 1 mg/kg or placebo every 6 weeks for up to 18 doses; all participants received pembrolizumab 200 mg every 3 weeks for up to 35 doses. Primary end points were overall survival and progression-free survival. RESULTS: Of the 568 participants, 284 were randomly allocated to each group. Median overall survival was 21.4 months for pembrolizumab-ipilimumab versus 21.9 months for pembrolizumab-placebo (hazard ratio, 1.08; 95% CI, 0.85 to 1.37; P = .74). Median progression-free survival was 8.2 months for pembrolizumab-ipilimumab versus 8.4 months for pembrolizumab-placebo (hazard ratio, 1.06; 95% CI, 0.86 to 1.30; P = .72). Grade 3-5 adverse events occurred in 62.4% of pembrolizumab-ipilimumab recipients versus 50.2% of pembrolizumab-placebo recipients and led to death in 13.1% versus 7.5%. The external data and safety monitoring committee recommended that the study be stopped for futility and that participants discontinue ipilimumab and placebo. CONCLUSION: Adding ipilimumab to pembrolizumab does not improve efficacy and is associated with greater toxicity than pembrolizumab monotherapy as first-line treatment for metastatic NSCLC with PD-L1 TPS ≥ 50% and no targetable EGFR or ALK aberrations. These data do not support use of pembrolizumab-ipilimumab in place of pembrolizumab monotherapy in this population.
RCT Entities:
PURPOSE:Pembrolizumab monotherapy is standard first-line therapy for metastatic non-small-cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1) tumor proportion score (TPS) ≥ 50% without actionable driver mutations. It is not known whether adding ipilimumab to pembrolizumab improves efficacy over pembrolizumab alone in this population. METHODS: In the randomized, double-blind, phase III KEYNOTE-598 trial (ClinicalTrials.gov identifier: NCT03302234), eligible patients with previously untreated metastatic NSCLC with PD-L1 TPS ≥ 50% and no sensitizing EGFR or ALK aberrations were randomly allocated 1:1 to ipilimumab 1 mg/kg or placebo every 6 weeks for up to 18 doses; all participants received pembrolizumab 200 mg every 3 weeks for up to 35 doses. Primary end points were overall survival and progression-free survival. RESULTS: Of the 568 participants, 284 were randomly allocated to each group. Median overall survival was 21.4 months for pembrolizumab-ipilimumab versus 21.9 months for pembrolizumab-placebo (hazard ratio, 1.08; 95% CI, 0.85 to 1.37; P = .74). Median progression-free survival was 8.2 months for pembrolizumab-ipilimumab versus 8.4 months for pembrolizumab-placebo (hazard ratio, 1.06; 95% CI, 0.86 to 1.30; P = .72). Grade 3-5 adverse events occurred in 62.4% of pembrolizumab-ipilimumab recipients versus 50.2% of pembrolizumab-placebo recipients and led to death in 13.1% versus 7.5%. The external data and safety monitoring committee recommended that the study be stopped for futility and that participants discontinue ipilimumab and placebo. CONCLUSION: Adding ipilimumab to pembrolizumab does not improve efficacy and is associated with greater toxicity than pembrolizumab monotherapy as first-line treatment for metastatic NSCLC with PD-L1 TPS ≥ 50% and no targetable EGFR or ALK aberrations. These data do not support use of pembrolizumab-ipilimumab in place of pembrolizumab monotherapy in this population.
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