KEYNOTE-033: Randomized phase 3 study of pembrolizumab vs docetaxel in previously treated,PD-L1-positive,advanced NSCLC |
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| Authors: | Shengxiang Ren Jifeng Feng Shenglin Ma HuaJun Chen Zhiyong Ma Cheng Huang Li Zhang Jianxing He Changli Wang Jianying Zhou Pongwut Danchaivijitr Chin-Chou Wang Ihor Vynnychenko Kai Wang Francisco Orlandi Virote Sriuranpong Ben Li Jun Ge Thao Dang Caicun Zhou |
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| Institution: | 1. Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China;2. Oncology Department, Jiangsu Cancer Hospital, Nanjing, China;3. Department of Thoracic Oncology, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Zhejiang University Cancer Center, Zhejiang, People's Republic of China;4. Guangdong Provincial People's Hospital, Guangdong Lung Cancer Institute, Guangzhou, China;5. Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University/Henan Cancer Hospital, Zhengzhou, China;6. Department of Pneumology, Fujian Provincial Cancer Hospital, Fuzhou, China;7. Cancer Center, Sun Yat-Sen University, Guangzhou, China;8. Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China;9. Department of Biotherapy 17F, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China;10. Department of Respiratory Medicine, The First Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou, China;11. Division of Medical Oncology, Siriraj Hospital, Bangkok, Thailand;12. Chang Gung Medical Foundation, Kaohsiung, Taiwan;13. RMI Sumy Regional Clinical Oncology Dispensary, Sumy State University, Sumy, Ukraine;14. Department of Respiration Medicine, The Second Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou, China;15. Region Metropolitana de Santiago, Orlandi Oncologia, Providencia, Chile;16. Medical Oncology Unit, King Chulalongkorn Memorial Hospital, Bangkok, Thailand;17. MSD China, Beijing, China;18. MSD China, Shanghai, China;19. Merck & Co., Inc., Rahway, NJ, USA |
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| Abstract: | KEYNOTE-033 (NCT02864394) was a multicountry, open-label, phase 3 study that compared pembrolizumab vs docetaxel in previously treated, programmed death-ligand 1 (PD-L1)-positive, advanced non-small cell lung cancer (NSCLC), with most patients enrolled in mainland China. Eligible patients were randomized (1:1) to pembrolizumab 2 mg/kg or docetaxel 75 mg/m2 every 3 weeks. Primary endpoints were overall survival (OS) and progression-free survival and were evaluated sequentially using stratified log-rank tests, first in patients with PD-L1 tumor proportion score (TPS) ≥50% and then in patients with PD-L1 TPS ≥1% (significance threshold: P < .025, one-sided). A total of 425 patients were randomized to pembrolizumab (N = 213) or docetaxel (N = 212) between 8 September 2016 and 17 October 2018. In patients with a PD-L1 TPS ≥50% (n = 227), median OS was 12.3 months with pembrolizumab and 10.9 months with docetaxel; the hazard ratio (HR) was 0.83 (95% confidence interval CI]: 0.61-1.14; P = .1276). Because the significance threshold was not met, sequential testing of OS and PFS was ceased. In patients with a PD-L1 TPS ≥1%, the HR for OS for pembrolizumab vs docetaxel was 0.75 (95% CI: 0.60-0.95). In patients from mainland China (n = 311) with a PD-L1 TPS ≥1%, HR for OS was 0.68 (95% CI: 0.51-0.89). Incidence of grade 3 to 5 treatment-related AEs was 11.3% with pembrolizumab vs 47.5% with docetaxel. In summary, pembrolizumab improved OS vs docetaxel in previously treated, PD-L1-positive NSCLC without unexpected safety signals; although the statistical significance threshold was not reached, the numerical improvement is consistent with that previously observed for pembrolizumab in previously treated, advanced NSCLC. |
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| Keywords: | immunotherapy NSCLC pembrolizumab programmed death 1 programmed death-ligand 1 |
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