Roy S Herbst1, Edward B Garon2, Dong-Wan Kim3, Byoung Chul Cho4, Radj Gervais5, Jose L Perez-Gracia6, Ji-Youn Han7, Margarita Majem8, Martin D Forster9, Isabelle Monnet10, Silvia Novello11, Matthew A Gubens12, Michael Boyer13, Wu-Chou Su14, Ayman Samkari15, Erin H Jensen15, Julie Kobie15, Bilal Piperdi15, Paul Baas16. 1. Section of Medical Oncology, Yale Comprehensive Cancer Center, Yale University School of Medicine, New Haven, Connecticut. Electronic address: roy.herbst@yale.edu. 2. David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California. 3. Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea. 4. Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea. 5. Centre François Baclesse, Caen, France. 6. Clinica Universidad de Navarra, Pamplona, Spain. 7. Center for Lung Cancer, National Cancer Center, Goyang, South Korea. 8. Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 9. UCL Cancer Institute/University College London Hospitals, London, United Kingdom. 10. Centre Hospitalier Intercommunal de Créteil, Créteil, France. 11. Department of Oncology, University of Turin, Azienda Ospedaliero Universitaria San Luigi, Turin, Italy. 12. University of California, San Francisco, San Francisco, California. 13. Chris O'Brien Lifehouse, Camperdown, Australia. 14. National Cheng Kung University Hospital, Tainan, Taiwan. 15. Merck & Co., Inc., Kenilworth, New Jersey. 16. The Netherlands Cancer Institute, Amsterdam, the Netherlands.
Abstract
INTRODUCTION: In the KEYNOTE-010 study, pembrolizumab improved overall survival (OS) versus docetaxel in patients with previously treated, advanced NSCLC with programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) ≥50% and ≥1%. We report 5-year efficacy and safety follow-up for the KEYNOTE-010 study. METHODS: Patients were randomized to pembrolizumab 2 mg/kg or 10 mg/kg once every 3 weeks or docetaxel 75 mg/m2 once every 3 weeks for up to 35 cycles (2 y). Patients who completed pembrolizumab treatment and subsequently had recurrence could receive second-course pembrolizumab for up to 17 cycles (1 y). Pembrolizumab doses were pooled in this analysis. RESULTS: A total of 1034 patients were randomized (pembrolizumab, n = 691; docetaxel, n = 343). Median study follow-up was 67.4 months (range: 60.0‒77.9). The hazard ratio (95% confidence interval) for OS was 0.55 (0.44‒0.69) for patients with PD-L1 TPS ≥50% and 0.70 (0.61‒0.80) with PD-L1 TPS ≥1%. The 5-year OS rates for pembrolizumab versus docetaxel were 25.0% versus 8.2% in patients with PD-L1 TPS ≥50% and 15.6% versus 6.5% with PD-L1 TPS ≥1%. Among 79 patients who completed 35 cycles/2 years of pembrolizumab, the OS rate 3 years after completion (∼5 y from randomization) was 83.0%. A total of 21 patients received second-course pembrolizumab; 11 (52.4%) had an objective response after starting the second course and 15 (71.4%) were alive at data cutoff. Exploratory biomarker analysis revealed that higher tissue tumor mutational burden (≥175 mutations per exome) was associated with improved outcomes with pembrolizumab. CONCLUSIONS: Pembrolizumab continued to provide long-term benefit than docetaxel in patients with previously treated advanced NSCLC with PD-L1 TPS ≥50% and ≥1%. Our findings confirm pembrolizumab as a standard-of-care treatment in the second-line or later setting.
INTRODUCTION: In the KEYNOTE-010 study, pembrolizumab improved overall survival (OS) versus docetaxel in patients with previously treated, advanced NSCLC with programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) ≥50% and ≥1%. We report 5-year efficacy and safety follow-up for the KEYNOTE-010 study. METHODS: Patients were randomized to pembrolizumab 2 mg/kg or 10 mg/kg once every 3 weeks or docetaxel 75 mg/m2 once every 3 weeks for up to 35 cycles (2 y). Patients who completed pembrolizumab treatment and subsequently had recurrence could receive second-course pembrolizumab for up to 17 cycles (1 y). Pembrolizumab doses were pooled in this analysis. RESULTS: A total of 1034 patients were randomized (pembrolizumab, n = 691; docetaxel, n = 343). Median study follow-up was 67.4 months (range: 60.0‒77.9). The hazard ratio (95% confidence interval) for OS was 0.55 (0.44‒0.69) for patients with PD-L1 TPS ≥50% and 0.70 (0.61‒0.80) with PD-L1 TPS ≥1%. The 5-year OS rates for pembrolizumab versus docetaxel were 25.0% versus 8.2% in patients with PD-L1 TPS ≥50% and 15.6% versus 6.5% with PD-L1 TPS ≥1%. Among 79 patients who completed 35 cycles/2 years of pembrolizumab, the OS rate 3 years after completion (∼5 y from randomization) was 83.0%. A total of 21 patients received second-course pembrolizumab; 11 (52.4%) had an objective response after starting the second course and 15 (71.4%) were alive at data cutoff. Exploratory biomarker analysis revealed that higher tissue tumor mutational burden (≥175 mutations per exome) was associated with improved outcomes with pembrolizumab. CONCLUSIONS: Pembrolizumab continued to provide long-term benefit than docetaxel in patients with previously treated advanced NSCLC with PD-L1 TPS ≥50% and ≥1%. Our findings confirm pembrolizumab as a standard-of-care treatment in the second-line or later setting.
Authors: Rianne D W Vaes; Kobe Reynders; Jenny Sprooten; Kathleen T Nevola; Kasper M A Rouschop; Marc Vooijs; Abhishek D Garg; Maarten Lambrecht; Lizza E L Hendriks; Marijana Rucevic; Dirk De Ruysscher Journal: Cancers (Basel) Date: 2021-12-13 Impact factor: 6.639