Tislelizumab Versus Docetaxel in Patients With Previously Treated Advanced NSCLC (RATIONALE-303): A Phase 3, Open-Label,Randomized Controlled Trial |
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| Affiliation: | 1. Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China;2. Department of Thoracic Medical Oncology, Lung Cancer Diagnosis and Treatment Centre, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Centre for Cancer, Tianjin, People’s Republic of China;3. Department of Thoracic Medical Oncology, Cancer Hospital of University of Chinese Academy of Sciences and Zhejiang Cancer Hospital, Hangzhou, People’s Republic of China;4. The First Hospital of China Medical University, Shenyang, People’s Republic of China;5. Department of Oncology, Jiangsu Province Hospital, Nanjing, People’s Republic of China;6. The Affiliated Cancer Hospital of Zhengzhou University/Henan Cancer Hospital, Zhengzhou, People’s Republic of China;7. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Thoracic Medical Oncology, Peking University Cancer Hospital and Institute, Beijing, People’s Republic of China;8. Department of Medical Thoracic Oncology, Jilin Cancer Hospital, Changchun, People’s Republic of China;9. State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China;10. Hubei Cancer Hospital, Wuhan, People’s Republic of China;11. Jiangxi Cancer Hospital, Nanchang, People’s Republic of China;12. Clinical Center Vitamed and Sechenov University, Moscow, Russia;13. Acibadem Health Group- Adana Acibadem Hospital/Medical Oncology, Adana, Turkey;14. Pavlov First State Medical University, Saint-Petersburg, Russia;15. BHI of Omsk Region Clinical Oncology Dispensary, Omsk, Russia;p. BeiGene (Beijing) Co., Ltd., Beijing, People’s Republic of China;q. BeiGene USA, Inc., Emeryville, California;r. Department of Cancer and Blood, Auckland City Hospital, Auckland, New Zealand |
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| Abstract: | IntroductionThe phase 3 RATIONALE-303 trial (NCT03358875) investigated the efficacy and safety of tislelizumab versus docetaxel in pretreated patients with advanced NSCLC. Here, we report the efficacy and safety results and describe the exploratory biomarker analyses.MethodsA total of 805 patients aged more than or equal to 18 years with locally advanced or metastatic squamous or nonsquamous NSCLC were randomized 2:1 to intravenous tislelizumab 200 mg or docetaxel 75 mg/m2 every 3 weeks. Co-primary end points were overall survival (OS) in the intent-to-treat (ITT) and programmed death-ligand 1 (PD-L1) tumor cell expression greater than or equal to 25% populations. The exploratory biomarker analyses included PD-L1 expression, tumor mutation burden, and gene expression profile.ResultsAt the prespecified interim analysis (August 10, 2020), the co-primary end point of OS in the ITT population was met, with a statistically significant and clinically meaningful improvement in OS with tislelizumab versus docetaxel (median 17.2 versus 11.9 mo, respectively; hazard ratio [HR] = 0.64, p < 0.0001). At the final analysis (July 15, 2021), the other co-primary end point of OS in the PD-L1 tumor cell greater than or equal to 25% population was further met (median 19.3 versus 11.5 mo, respectively; HR = 0.53, p < 0.0001), and OS continued to improve in the ITT population (median 16.9 versus 11.9 mo, respectively, HR = 0.66). Exploratory biomarker analyses revealed the potential association of NOTCH1–4 mutations with improved tislelizumab efficacy for both OS and progression-free survival, whereas tissue tumor mutation burden correlated with progression-free survival benefit, but not OS benefit. No new safety signals were identified.ConclusionsTislelizumab was found to have a significantly improved and long-term clinical benefit in OS versus docetaxel in pretreated patients with advanced NSCLC, regardless of PD-L1 expression. |
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| Keywords: | Tislelizumab Docetaxel Non–small cell lung cancer Randomized clinical trial |
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