Ying Cheng MD , Yun Fan MD , Yanqiu Zhao MD , Dingzhi Huang MD , Xingya Li MD , Peng Zhang MD , Mafei Kang MD , Nong Yang MD , Diansheng Zhong MD , Zhen Wang MD , Yan Yu MD , Yu Zhang MD , Jun Zhao MD , Tai Qin MD , Chenqi Chen MS , Shiangjiin Leaw MD , Wenjuan Zheng MD , Yong Song MD , RATIONALE-312 Study Group
{"title":"Tislelizumab 联合铂类和依托泊苷与安慰剂联合铂类和依托泊苷作为广泛期小细胞肺癌一线治疗（RATIONALE-312）：一项多中心、双盲、安慰剂对照、随机、3 期临床试验。","authors":"Ying Cheng MD , Yun Fan MD , Yanqiu Zhao MD , Dingzhi Huang MD , Xingya Li MD , Peng Zhang MD , Mafei Kang MD , Nong Yang MD , Diansheng Zhong MD , Zhen Wang MD , Yan Yu MD , Yu Zhang MD , Jun Zhao MD , Tai Qin MD , Chenqi Chen MS , Shiangjiin Leaw MD , Wenjuan Zheng MD , Yong Song MD , RATIONALE-312 Study Group","doi":"10.1016/j.jtho.2024.03.008","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><p>Extensive-stage SCLC (ES-SCLC) prognosis remains poor. The phase 3 RATIONALE-312 study aimed to evaluate the efficacy and safety of tislelizumab plus chemotherapy as first-line treatment for ES-SCLC.</p></div><div><h3>Methods</h3><p>RATIONALE-312 is a randomized, double-blind, placebo-controlled trial, conducted in the People's Republic of China. Eligible patients with previously untreated ES-SCLC were randomized 1:1 to receive four cycles of tislelizumab 200 mg or placebo, with etoposide plus carboplatin or cisplatin intravenously every 3 weeks, followed by tislelizumab 200 mg or placebo as maintenance. The primary end point was overall survival (OS). Secondary end points included progression-free survival and safety.</p></div><div><h3>Results</h3><p>Between July 22, 2019 and April 21, 2021, 457 patients were randomized to tislelizumab (n = 227) or placebo (n = 230), plus chemotherapy. Baseline demographics were generally balanced between arms. At the data cutoff (April 19, 2023), the median study follow-up was 14.2 months (interquartile range: 8.6–25.3). Tislelizumab plus chemotherapy exhibited a statistically significant OS benefit versus placebo plus chemotherapy (stratified hazard ratio = 0.75 [95% confidence interval (CI): 0.61–0.93]; one-sided <em>p</em> = 0.0040; median: 15.5 [95% CI: 13.5–17.1] versus 13.5 mo [95% CI: 12.1–14.9], respectively). Progression-free survival was significantly improved in the tislelizumab versus placebo arm (stratified hazard ratio = 0.64 [95% CI: 0.52–0.78]; <em>p</em> < 0.0001; median: 4.7 [95% CI: 4.3–5.5] versus 4.3 mo [95% CI: 4.2–4.4], respectively). Grade greater than or equal to 3 treatment-related adverse events were reported in 86% of patients in each treatment arm and were mostly hematologic.</p></div><div><h3>Conclusions</h3><p>Tislelizumab plus chemotherapy exhibited statistically significant clinical benefit and manageable safety compared with placebo plus chemotherapy as first-line treatment in patients with advanced ES-SCLC.</p></div>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":null,"pages":null},"PeriodicalIF":21.0000,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1556086424001151/pdfft?md5=b31c77f12e1d6962568f15faab6d5da6&pid=1-s2.0-S1556086424001151-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Tislelizumab Plus Platinum and Etoposide Versus Placebo Plus Platinum and Etoposide as First-Line Treatment for Extensive-Stage SCLC (RATIONALE-312): A Multicenter, Double-Blind, Placebo-Controlled, Randomized, Phase 3 Clinical Trial\",\"authors\":\"Ying Cheng MD , Yun Fan MD , Yanqiu Zhao MD , Dingzhi Huang MD , Xingya Li MD , Peng Zhang MD , Mafei Kang MD , Nong Yang MD , Diansheng Zhong MD , Zhen Wang MD , Yan Yu MD , Yu Zhang MD , Jun Zhao MD , Tai Qin MD , Chenqi Chen MS , Shiangjiin Leaw MD , Wenjuan Zheng MD , Yong Song MD , RATIONALE-312 Study Group\",\"doi\":\"10.1016/j.jtho.2024.03.008\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Introduction</h3><p>Extensive-stage SCLC (ES-SCLC) prognosis remains poor. The phase 3 RATIONALE-312 study aimed to evaluate the efficacy and safety of tislelizumab plus chemotherapy as first-line treatment for ES-SCLC.</p></div><div><h3>Methods</h3><p>RATIONALE-312 is a randomized, double-blind, placebo-controlled trial, conducted in the People's Republic of China. Eligible patients with previously untreated ES-SCLC were randomized 1:1 to receive four cycles of tislelizumab 200 mg or placebo, with etoposide plus carboplatin or cisplatin intravenously every 3 weeks, followed by tislelizumab 200 mg or placebo as maintenance. The primary end point was overall survival (OS). Secondary end points included progression-free survival and safety.</p></div><div><h3>Results</h3><p>Between July 22, 2019 and April 21, 2021, 457 patients were randomized to tislelizumab (n = 227) or placebo (n = 230), plus chemotherapy. Baseline demographics were generally balanced between arms. At the data cutoff (April 19, 2023), the median study follow-up was 14.2 months (interquartile range: 8.6–25.3). Tislelizumab plus chemotherapy exhibited a statistically significant OS benefit versus placebo plus chemotherapy (stratified hazard ratio = 0.75 [95% confidence interval (CI): 0.61–0.93]; one-sided <em>p</em> = 0.0040; median: 15.5 [95% CI: 13.5–17.1] versus 13.5 mo [95% CI: 12.1–14.9], respectively). Progression-free survival was significantly improved in the tislelizumab versus placebo arm (stratified hazard ratio = 0.64 [95% CI: 0.52–0.78]; <em>p</em> < 0.0001; median: 4.7 [95% CI: 4.3–5.5] versus 4.3 mo [95% CI: 4.2–4.4], respectively). Grade greater than or equal to 3 treatment-related adverse events were reported in 86% of patients in each treatment arm and were mostly hematologic.</p></div><div><h3>Conclusions</h3><p>Tislelizumab plus chemotherapy exhibited statistically significant clinical benefit and manageable safety compared with placebo plus chemotherapy as first-line treatment in patients with advanced ES-SCLC.</p></div>\",\"PeriodicalId\":17515,\"journal\":{\"name\":\"Journal of Thoracic Oncology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":21.0000,\"publicationDate\":\"2024-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S1556086424001151/pdfft?md5=b31c77f12e1d6962568f15faab6d5da6&pid=1-s2.0-S1556086424001151-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Thoracic Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1556086424001151\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Thoracic Oncology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1556086424001151","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
Tislelizumab Plus Platinum and Etoposide Versus Placebo Plus Platinum and Etoposide as First-Line Treatment for Extensive-Stage SCLC (RATIONALE-312): A Multicenter, Double-Blind, Placebo-Controlled, Randomized, Phase 3 Clinical Trial
Introduction
Extensive-stage SCLC (ES-SCLC) prognosis remains poor. The phase 3 RATIONALE-312 study aimed to evaluate the efficacy and safety of tislelizumab plus chemotherapy as first-line treatment for ES-SCLC.
Methods
RATIONALE-312 is a randomized, double-blind, placebo-controlled trial, conducted in the People's Republic of China. Eligible patients with previously untreated ES-SCLC were randomized 1:1 to receive four cycles of tislelizumab 200 mg or placebo, with etoposide plus carboplatin or cisplatin intravenously every 3 weeks, followed by tislelizumab 200 mg or placebo as maintenance. The primary end point was overall survival (OS). Secondary end points included progression-free survival and safety.
Results
Between July 22, 2019 and April 21, 2021, 457 patients were randomized to tislelizumab (n = 227) or placebo (n = 230), plus chemotherapy. Baseline demographics were generally balanced between arms. At the data cutoff (April 19, 2023), the median study follow-up was 14.2 months (interquartile range: 8.6–25.3). Tislelizumab plus chemotherapy exhibited a statistically significant OS benefit versus placebo plus chemotherapy (stratified hazard ratio = 0.75 [95% confidence interval (CI): 0.61–0.93]; one-sided p = 0.0040; median: 15.5 [95% CI: 13.5–17.1] versus 13.5 mo [95% CI: 12.1–14.9], respectively). Progression-free survival was significantly improved in the tislelizumab versus placebo arm (stratified hazard ratio = 0.64 [95% CI: 0.52–0.78]; p < 0.0001; median: 4.7 [95% CI: 4.3–5.5] versus 4.3 mo [95% CI: 4.2–4.4], respectively). Grade greater than or equal to 3 treatment-related adverse events were reported in 86% of patients in each treatment arm and were mostly hematologic.
Conclusions
Tislelizumab plus chemotherapy exhibited statistically significant clinical benefit and manageable safety compared with placebo plus chemotherapy as first-line treatment in patients with advanced ES-SCLC.
期刊介绍：
Journal of Thoracic Oncology (JTO), the official journal of the International Association for the Study of Lung Cancer,is the primary educational and informational publication for topics relevant to the prevention, detection, diagnosis, and treatment of all thoracic malignancies.The readship includes epidemiologists, medical oncologists, radiation oncologists, thoracic surgeons, pulmonologists, radiologists, pathologists, nuclear medicine physicians, and research scientists with a special interest in thoracic oncology.
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