Roy S Herbst1, Edward B Garon2, Dong-Wan Kim3, Byoung Chul Cho4, Jose L Perez-Gracia5, Ji-Youn Han6, Catherine Dubos Arvis7, Margarita Majem8, Martin D Forster9, Isabelle Monnet10, Silvia Novello11, Zsuzsanna Szalai12, Matthew A Gubens13, Wu-Chou Su14, Giovanni Luca Ceresoli15, Ayman Samkari16, Erin H Jensen16, Gregory M Lubiniecki16, Paul Baas17. 1. Department of Medical Oncology, Yale University School of Medicine, Yale Comprehensive Cancer Center, New Haven, CT. 2. David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA. 3. Seoul National University Hospital, Seoul, South Korea. 4. Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea. 5. Clinica Universidad de Navarra, Pamplona, Spain. 6. National Cancer Center, Korea, Goyang-si, South Korea. 7. Centre François Baclesse, Caen, France. 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. University of Turin, Azienda Ospedaliero-Universitaria San Luigi Gonzaga, Orbassano, Italy. 12. Petz Aladár County Teaching Hospital, Györ, Hungary. 13. University of California, San Francisco, San Francisco, CA. 14. National Cheng Kung University Hospital, Tainan, Taiwan, Republic of China. 15. Cliniche Humanitas Gavazzeni, Bergamo, Italy. 16. Merck & Co, Kenilworth, NJ. 17. The Netherlands Cancer Institute, Amsterdam, the Netherlands.
Abstract
PURPOSE: In the KEYNOTE-010 study, pembrolizumab improved overall survival (OS) versus docetaxel in previously treated, programmed death-ligand 1 (PD-L1)‒expressing advanced non‒small-cell lung cancer (NSCLC) in patients with a tumor proportion score (TPS) ≥ 50% and ≥ 1%. We report KEYNOTE-010 long-term outcomes, including after 35 cycles/2 years or second-course pembrolizumab. METHODS: Of 1,033 patients randomly assigned (intention to treat), 690 received up to 35 cycles/2 years ofpembrolizumab 2 mg/kg (n = 344) or 10 mg/kg (n = 346) every 3 weeks, and 343 received docetaxel 75 mg/m2 every 3 weeks. Eligible patients with disease progression after 35 cycles/2 years ofpembrolizumab could receive second-course treatment (up to 17 cycles). Pembrolizumab doses were pooled because no between-dose difference was observed at primary analysis. RESULTS:Pembrolizumab continued to improve OS over docetaxel in the PD-L1 TPS ≥ 50% and ≥ 1% groups (hazard ratio [HR], 0.53; 95% CI, 0.42 to 0.66; P < .00001; and HR, 0.69; 95% CI, 0.60 to 0.80; P < .00001, respectively) after a 42.6-month (range, 35.2-53.2 months) median follow-up. Estimated 36-month OS rates were 34.5% versus 12.7% and 22.9% versus 11.0%, respectively. Grade 3-5 treatment-related adverse events occurred in 16% versus 37% of patients, respectively. Seventy-nine of 690 patients completed 35 cycles/2 years of pembrolizumab; 12-monthOS and progression-free survival rates after completing treatment were 98.7% (95% CI, 91.1% to 99.8%) and 72.5% (95% CI, 59.9% to 81.8%), respectively. Seventy-five patients (95%) had objective response (RECIST v1.1, blinded independent central review) and 48 (64%) had ongoing response. Grade 3-5 treatment-related adverse events occurred in 17.7% of patients. Fourteen patients received second-course pembrolizumab: 5 completed 17 cycles, 6 (43%) had partial response, and 5 (36%) had stable disease. CONCLUSION:Pembrolizumab provided long-term OS benefit over docetaxel, with manageable safety, durable responses among patients receiving 2 years of treatment, and disease control with second-course treatment, further supporting pembrolizumab for previously treated, PD-L1‒expressing advanced NSCLC.
RCT Entities:
PURPOSE: In the KEYNOTE-010 study, pembrolizumab improved overall survival (OS) versus docetaxel in previously treated, programmed death-ligand 1 (PD-L1)‒expressing advanced non‒small-cell lung cancer (NSCLC) in patients with a tumor proportion score (TPS) ≥ 50% and ≥ 1%. We report KEYNOTE-010 long-term outcomes, including after 35 cycles/2 years or second-course pembrolizumab. METHODS: Of 1,033 patients randomly assigned (intention to treat), 690 received up to 35 cycles/2 years of pembrolizumab 2 mg/kg (n = 344) or 10 mg/kg (n = 346) every 3 weeks, and 343 received docetaxel 75 mg/m2 every 3 weeks. Eligible patients with disease progression after 35 cycles/2 years of pembrolizumab could receive second-course treatment (up to 17 cycles). Pembrolizumab doses were pooled because no between-dose difference was observed at primary analysis. RESULTS:Pembrolizumab continued to improve OS over docetaxel in the PD-L1 TPS ≥ 50% and ≥ 1% groups (hazard ratio [HR], 0.53; 95% CI, 0.42 to 0.66; P < .00001; and HR, 0.69; 95% CI, 0.60 to 0.80; P < .00001, respectively) after a 42.6-month (range, 35.2-53.2 months) median follow-up. Estimated 36-month OS rates were 34.5% versus 12.7% and 22.9% versus 11.0%, respectively. Grade 3-5 treatment-related adverse events occurred in 16% versus 37% of patients, respectively. Seventy-nine of 690 patients completed 35 cycles/2 years of pembrolizumab; 12-month OS and progression-free survival rates after completing treatment were 98.7% (95% CI, 91.1% to 99.8%) and 72.5% (95% CI, 59.9% to 81.8%), respectively. Seventy-five patients (95%) had objective response (RECIST v1.1, blinded independent central review) and 48 (64%) had ongoing response. Grade 3-5 treatment-related adverse events occurred in 17.7% of patients. Fourteen patients received second-course pembrolizumab: 5 completed 17 cycles, 6 (43%) had partial response, and 5 (36%) had stable disease. CONCLUSION:Pembrolizumab provided long-term OS benefit over docetaxel, with manageable safety, durable responses among patients receiving 2 years of treatment, and disease control with second-course treatment, further supporting pembrolizumab for previously treated, PD-L1‒expressing advanced NSCLC.
Authors: René J Boosman; Jacobus A Burgers; Egbert F Smit; Neeltje Steeghs; Anthonie J van der Wekken; Jos H Beijnen; Alwin D R Huitema; Rob Ter Heine Journal: Drugs Date: 2021-12-11 Impact factor: 9.546
Authors: Diego L Kaen; Nicolas Minatta; Alessandro Russo; Umberto Malapelle; Diego de Miguel-Pérez; Christian Rolfo Journal: Adv Exp Med Biol Date: 2021 Impact factor: 2.622
Authors: John M Varlotto; Zhuoxin Sun; Bonnie Ky; Jenica Upshaw; Sharyn I Katz; Thomas J Fitzgerald; Heather Wakelee; Maximilian Diehn; David A Mankoff; Christine Lovely; Chandra Belani; Kurt Oettel; Gregory Masters; Suresh Ramalingam; Nathan A Pennell Journal: Oncologist Date: 2021-03-11
Authors: Praful Ravi; Charlene Mantia; Christopher Su; Karl Sorenson; Dean Elhag; Nityam Rathi; Ziad Bakouny; Neeraj Agarwal; Yousef Zakharia; Brian A Costello; Rana R McKay; Vivek Narayan; Ajjai Alva; Bradley A McGregor; Xin Gao; David F McDermott; Toni K Choueiri Journal: JAMA Oncol Date: 2020-10-01 Impact factor: 31.777