Shun Lu1, Jie Wang2, Yan Yu3, Xinmin Yu4, Yanping Hu5, Xinghao Ai6, Zhiyong Ma7, Xingya Li8, Wu Zhuang9, Yunpeng Liu10, Weidong Li11, Jiuwei Cui12, Dong Wang13, Wangjun Liao14, Jianying Zhou15, Zhehai Wang16, Yuping Sun17, Xiusong Qiu18, Jie Gao19, Yuanyuan Bao20, Liang Liang21, Mengzhao Wang22. 1. Shanghai Chest Hospital, Department of Oncology, Shanghai, People's Republic of China. Electronic address: shunlu@sjtu.edu.cn. 2. Cancer Hospital Chinese Academy of Medical Sciences, Beijing, Department of Medical Oncology, People's Republic of China. 3. Harbin Medical University Cancer Hospital, Department of Thoracic Oncology, Harbin, People's Republic of China. 4. Zhejiang Cancer Hospital, Department of Thoracic Oncology, Hangzhou, People's Republic of China. 5. Hubei Cancer Hospital, Department of Thoracic Oncology, Wuhan, People's Republic of China. 6. Shanghai Chest Hospital, Department of Oncology, Shanghai, People's Republic of China. 7. The Affiliated Cancer Hospital of Zhengzhou University/Henan Cancer Hospital, Department of Medical Oncology, Zhengzhou, People's Republic of China. 8. The First Affiliated Hospital of Zhengzhou University, Department of Oncology, Zhengzhou, People's Republic of China. 9. Fujian Cancer Hospital, Department of Medical Oncology, Fuzhou, People's Republic of China. 10. The First Hospital of China Medical University, Department of Medical Oncology, Shenyang, People's Republic of China. 11. Cancer Center of Guangzhou Medical University, Cancer Center Department, Guangzhou, People's Republic of China. 12. The First Hospital of Jilin University, Cancer Center Department, Changchun, People's Republic of China. 13. Daping Hospital, Third Military Medical University, Cancer Center Department, Chongqing, People's Republic of China. 14. Nanfang Hospital of Southern Medical University, Department of Oncology, Guangzhou, People's Republic of China. 15. The First Affiliated Hospital of Zhejiang University, Department of Respiratory Disease, Hangzhou, People's Republic of China. 16. Shandong Cancer Hospital, Department of Internal Medicine-Oncology, Jinan, People's Republic of China. 17. Jinan Central Hospital, Department of Oncology, Jinan, People's Republic of China. 18. BeiGene (Beijing) Co., Ltd., Department of Clinical Development, Beijing, People's Republic of China. 19. BeiGene (Beijing) Co., Ltd., Beijing, People's Republic of China. 20. BeiGene (Beijing) Co., Ltd., Department of Medical Oncology, Beijing, People's Republic of China. 21. BeiGene (Beijing) Co., Ltd., Department of Clinical Biomarkers, Beijing, People's Republic of China. 22. Peking Union Medical College Hospital, Department of Pulmonary Medicine, Beijing, People's Republic of China.
Abstract
INTRODUCTION:Tislelizumab, an anti-programmed cell death protein-1 antibody, was specifically engineered to minimize FcɣR macrophage binding to abrogate antibody-dependent phagocytosis. Compared with chemotherapy alone, tislelizumab plus chemotherapy may improve clinical outcomes in patients with advanced nonsquamous NSCLC (nsq-NSCLC). METHODS: In this open-label phase 3 trial (RATIONALE 304; NCT03663205), patients with histologically confirmed stage IIIB or IV nsq-NSCLC were randomized (2:1) to receive either arm A: tislelizumab plus platinum (carboplatin or cisplatin) and pemetrexed every 3 weeks (Q3Ws) or arm B: platinum and pemetrexed alone Q3W during induction treatment, followed by intravenous maintenance pemetrexed Q3W. The primary end point was progression-free survival (PFS) assessed by an independent review committee; clinical response and safety and tolerability were secondary end points. RESULTS: Overall, 332 patients (n = 222 [A]; n = 110 [B]) received treatment. With a median study follow-up of 9.8 months, PFS was significantly longer with tislelizumab plus chemotherapy compared with chemotherapy alone (median PFS: 9.7 versus 7.6 mo; hazard ratio = 0.645 [95% confidence interval: 0.462-0.902], p = 0.0044). In addition, response rates were higher and response duration was longer with combination therapy versus chemotherapy alone. Hematologic adverse events (AEs) were common in both treatment arms; the most reported AEs were grades 1 to 2 in severity. The most common grade greater than or equal to 3 AEs were associated with chemotherapy and included neutropenia (44.6% [A]; 35.5% [B]) and leukopenia (21.6% [A]; 14.5% [B]). CONCLUSIONS: Addition of tislelizumab to chemotherapy resulted in significantly prolonged PFS, higher response rates, and longer response duration compared with chemotherapy alone, identifying a new potential option for first-line treatment of advanced nsq-NSCLC irrespective of disease stage.
RCT Entities:
INTRODUCTION:Tislelizumab, an anti-programmed cell death protein-1 antibody, was specifically engineered to minimize FcɣR macrophage binding to abrogate antibody-dependent phagocytosis. Compared with chemotherapy alone, tislelizumab plus chemotherapy may improve clinical outcomes in patients with advanced nonsquamous NSCLC (nsq-NSCLC). METHODS: In this open-label phase 3 trial (RATIONALE 304; NCT03663205), patients with histologically confirmed stage IIIB or IV nsq-NSCLC were randomized (2:1) to receive either arm A: tislelizumab plus platinum (carboplatin or cisplatin) and pemetrexed every 3 weeks (Q3Ws) or arm B: platinum and pemetrexed alone Q3W during induction treatment, followed by intravenous maintenance pemetrexed Q3W. The primary end point was progression-free survival (PFS) assessed by an independent review committee; clinical response and safety and tolerability were secondary end points. RESULTS: Overall, 332 patients (n = 222 [A]; n = 110 [B]) received treatment. With a median study follow-up of 9.8 months, PFS was significantly longer with tislelizumab plus chemotherapy compared with chemotherapy alone (median PFS: 9.7 versus 7.6 mo; hazard ratio = 0.645 [95% confidence interval: 0.462-0.902], p = 0.0044). In addition, response rates were higher and response duration was longer with combination therapy versus chemotherapy alone. Hematologic adverse events (AEs) were common in both treatment arms; the most reported AEs were grades 1 to 2 in severity. The most common grade greater than or equal to 3 AEs were associated with chemotherapy and included neutropenia (44.6% [A]; 35.5% [B]) and leukopenia (21.6% [A]; 14.5% [B]). CONCLUSIONS: Addition of tislelizumab to chemotherapy resulted in significantly prolonged PFS, higher response rates, and longer response duration compared with chemotherapy alone, identifying a new potential option for first-line treatment of advanced nsq-NSCLC irrespective of disease stage.
Authors: M A Siciliano; G Caridà; D Ciliberto; M d'Apolito; C Pelaia; D Caracciolo; C Riillo; P Correale; A Galvano; A Russo; V Barbieri; P Tassone; P Tagliaferri Journal: ESMO Open Date: 2022-04-12