論文 - 詳細
| RRC ID | 86435 |
|---|---|
| 著者 | Wang H, Yao Z, Kang K, Zhou L, Xiu W, Sun J, Xie C, Yu M, Li Y, Zhang Y, Zheng Y, Lin G, Pan X, Wu Y, Luo R, Wang L, Tang M, Liao S, Zhu J, Zhou X, Zhang X, Xu Y, Liu Y, Peng F, Wang J, Xiang L, Yin L, Deng L, Huang M, Gong Y, Zou B, Wang H, Wu L, Yuan Z, Bi N, Fan M, Xu Y, Tong R, Yi L, Gan L, Xue J, Mo X, Chen C, Na F, Lu Y. |
| タイトル | Preclinical study and phase II trial of adapting low-dose radiotherapy to immunotherapy in small cell lung cancer. |
| ジャーナル | Med |
| Abstract |
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). |
| 巻・号 | 5(10) |
| ページ | 1237-1254.e9 |
| 公開日 | 2024-10-11 |
| DOI | 10.1016/j.medj.2024.06.002 |
| PII | S2666-6340(24)00248-4 |
| PMID | 38964333 |
| MeSH | Aged Animals Combined Modality Therapy Female Humans Immune Checkpoint Inhibitors* / pharmacology Immune Checkpoint Inhibitors* / therapeutic use Immunotherapy* / methods Lung Neoplasms* / immunology Lung Neoplasms* / mortality Lung Neoplasms* / pathology Lung Neoplasms* / radiotherapy Lung Neoplasms* / therapy Male Mice Middle Aged Progression-Free Survival Prospective Studies Radiotherapy Dosage Small Cell Lung Carcinoma* / immunology Small Cell Lung Carcinoma* / mortality Small Cell Lung Carcinoma* / pathology Small Cell Lung Carcinoma* / radiotherapy Small Cell Lung Carcinoma* / therapy Tumor Microenvironment / drug effects Tumor Microenvironment / immunology |
| リソース情報 | |
| 実験動物マウス | RBRC05737 |