Hui Wang, Zhuoran Yao, Kai Kang, Lin Zhou, Weigang Xiu, Jianguo Sun, Conghua Xie, Min Yu, Yanying Li, Yan Zhang, Yue Zheng, Guo Lin, Xiangyu Pan, Yijun Wu, Ren Luo, Laduona Wang, Min Tang, Shuangsi Liao, Jiang Zhu, Xiaojuan Zhou, Xuanwei Zhang, Yong Xu, Yongmei Liu, Feng Peng, Jin Wang, Lisha Xiang, Limei Yin, Lei Deng, Meijuan Huang, Youling Gong, Bingwen Zou, Hui Wang, Lin Wu, Zhiyong Yuan, Nan Bi, Min Fan, Yaping Xu, Ruizhan Tong, Linglu Yi, Lu Gan, Jianxin Xue, Xianming Mo, Chong Chen, Feifei Na, You Lu
{"title":"小细胞肺癌低剂量放射治疗与免疫治疗的临床前研究和 II 期试验。","authors":"Hui Wang, Zhuoran Yao, Kai Kang, Lin Zhou, Weigang Xiu, Jianguo Sun, Conghua Xie, Min Yu, Yanying Li, Yan Zhang, Yue Zheng, Guo Lin, Xiangyu Pan, Yijun Wu, Ren Luo, Laduona Wang, Min Tang, Shuangsi Liao, Jiang Zhu, Xiaojuan Zhou, Xuanwei Zhang, Yong Xu, Yongmei Liu, Feng Peng, Jin Wang, Lisha Xiang, Limei Yin, Lei Deng, Meijuan Huang, Youling Gong, Bingwen Zou, Hui Wang, Lin Wu, Zhiyong Yuan, Nan Bi, Min Fan, Yaping Xu, Ruizhan Tong, Linglu Yi, Lu Gan, Jianxin Xue, Xianming Mo, Chong Chen, Feifei Na, You Lu","doi":"10.1016/j.medj.2024.06.002","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) provide modest but unsatisfactory benefits for extensive-stage small cell lung cancer (ES-SCLC). Developing strategies for treating ES-SCLC is critical.</p><p><strong>Methods: </strong>We preliminarily explored the outcomes of salvage low-dose radiotherapy (LDRT) plus ICI on refractory SCLC patients. Next, we evaluated the combinational efficacy in murine SCLC. The tumor immune microenvironment (TIME) was analyzed for mechanistic study. Subsequently, we conducted a multicenter, prospective phase II trial that administered concurrent thoracic LDRT plus chemoimmunotherapy to treatment-naive ES-SCLC patients (MATCH trial, NCT04622228). The primary endpoint was confirmed objective response rate (ORR), and the key secondary endpoints included progression-free survival (PFS) and safety.</p><p><strong>Findings: </strong>Fifteen refractory SCLC patients treated with LDRT plus ICI were retrospectively reviewed. The ORR was 73.3% (95% confidence interval [CI], 44.9-92.2). We identified a specific dose of LDRT (15 Gy/5 fractions) that exhibited growth retardation and improved survival in murine SCLC when combined with ICIs. This combination recruited a special T cell population, TCF1<sup>+</sup> PD-1<sup>+</sup> CD8<sup>+</sup> stem-like T cells, from tumor-draining lymph nodes into the TIME. The MATCH trial showed a confirmed ORR of 87.5% (95% CI, 75.9-94.8). The median PFS was 6.9 months (95% CI, 5.4-9.3).</p><p><strong>Conclusions: </strong>These findings verified that LDRT plus chemoimmunotherapy was safe, feasible, and effective for ES-SCLC, warranting further investigation.</p><p><strong>Funding: </strong>This research was funded by West China Hospital (no. ZYJC21003), the National Natural Science Foundation of China (no. 82073336), and the MATCH trial was fully funded by Roche (China) Holding Ltd. (RCHL) and Shanghai Roche Pharmaceuticals Ltd. (SRPL).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8000,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Preclinical study and phase II trial of adapting low-dose radiotherapy to immunotherapy in small cell lung cancer.\",\"authors\":\"Hui Wang, Zhuoran Yao, Kai Kang, Lin Zhou, Weigang Xiu, Jianguo Sun, Conghua Xie, Min Yu, Yanying Li, Yan Zhang, Yue Zheng, Guo Lin, Xiangyu Pan, Yijun Wu, Ren Luo, Laduona Wang, Min Tang, Shuangsi Liao, Jiang Zhu, Xiaojuan Zhou, Xuanwei Zhang, Yong Xu, Yongmei Liu, Feng Peng, Jin Wang, Lisha Xiang, Limei Yin, Lei Deng, Meijuan Huang, Youling Gong, Bingwen Zou, Hui Wang, Lin Wu, Zhiyong Yuan, Nan Bi, Min Fan, Yaping Xu, Ruizhan Tong, Linglu Yi, Lu Gan, Jianxin Xue, Xianming Mo, Chong Chen, Feifei Na, You Lu\",\"doi\":\"10.1016/j.medj.2024.06.002\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) provide modest but unsatisfactory benefits for extensive-stage small cell lung cancer (ES-SCLC). Developing strategies for treating ES-SCLC is critical.</p><p><strong>Methods: </strong>We preliminarily explored the outcomes of salvage low-dose radiotherapy (LDRT) plus ICI on refractory SCLC patients. Next, we evaluated the combinational efficacy in murine SCLC. The tumor immune microenvironment (TIME) was analyzed for mechanistic study. Subsequently, we conducted a multicenter, prospective phase II trial that administered concurrent thoracic LDRT plus chemoimmunotherapy to treatment-naive ES-SCLC patients (MATCH trial, NCT04622228). The primary endpoint was confirmed objective response rate (ORR), and the key secondary endpoints included progression-free survival (PFS) and safety.</p><p><strong>Findings: </strong>Fifteen refractory SCLC patients treated with LDRT plus ICI were retrospectively reviewed. The ORR was 73.3% (95% confidence interval [CI], 44.9-92.2). 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Preclinical study and phase II trial of adapting low-dose radiotherapy to immunotherapy in small cell lung cancer.
Background: Immune checkpoint inhibitors (ICIs) provide modest but unsatisfactory benefits for extensive-stage small cell lung cancer (ES-SCLC). Developing strategies for treating ES-SCLC is critical.
Methods: We preliminarily explored the outcomes of salvage low-dose radiotherapy (LDRT) plus ICI on refractory SCLC patients. Next, we evaluated the combinational efficacy in murine SCLC. The tumor immune microenvironment (TIME) was analyzed for mechanistic study. Subsequently, we conducted a multicenter, prospective phase II trial that administered concurrent thoracic LDRT plus chemoimmunotherapy to treatment-naive ES-SCLC patients (MATCH trial, NCT04622228). The primary endpoint was confirmed objective response rate (ORR), and the key secondary endpoints included progression-free survival (PFS) and safety.
Findings: Fifteen refractory SCLC patients treated with LDRT plus ICI were retrospectively reviewed. The ORR was 73.3% (95% confidence interval [CI], 44.9-92.2). We identified a specific dose of LDRT (15 Gy/5 fractions) that exhibited growth retardation and improved survival in murine SCLC when combined with ICIs. This combination recruited a special T cell population, TCF1+ PD-1+ CD8+ stem-like T cells, from tumor-draining lymph nodes into the TIME. The MATCH trial showed a confirmed ORR of 87.5% (95% CI, 75.9-94.8). The median PFS was 6.9 months (95% CI, 5.4-9.3).
Conclusions: These findings verified that LDRT plus chemoimmunotherapy was safe, feasible, and effective for ES-SCLC, warranting further investigation.
Funding: This research was funded by West China Hospital (no. ZYJC21003), the National Natural Science Foundation of China (no. 82073336), and the MATCH trial was fully funded by Roche (China) Holding Ltd. (RCHL) and Shanghai Roche Pharmaceuticals Ltd. (SRPL).
期刊介绍：
Med is a flagship medical journal published monthly by Cell Press, the global publisher of trusted and authoritative science journals including Cell, Cancer Cell, and Cell Reports Medicine. Our mission is to advance clinical research and practice by providing a communication forum for the publication of clinical trial results, innovative observations from longitudinal cohorts, and pioneering discoveries about disease mechanisms. The journal also encourages thought-leadership discussions among biomedical researchers, physicians, and other health scientists and stakeholders. Our goal is to improve health worldwide sustainably and ethically.
Med publishes rigorously vetted original research and cutting-edge review and perspective articles on critical health issues globally and regionally. Our research section covers clinical case reports, first-in-human studies, large-scale clinical trials, population-based studies, as well as translational research work with the potential to change the course of medical research and improve clinical practice.
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