Low-dose radiotherapy concurrent with atezolizumab and chemotherapy as first-line treatment for extensive-stage small-cell lung cancer: 3-year follow-up of a multicenter, single-arm, phase 2 trial (MATCH)

Lin Zhou; Jianguo Sun; Conghua Xie; Kai Kang; Zhuoran Yao; Youling Gong; Meijuan Huang; Hui Wang; Lin Wu; Zhiyong Yuan; Nan Bi; Min Fan; Yaping Xu; Yao Chen; You Lu; MATCH study group

doi:10.1016/j.ijrobp.2025.06.3872

Low-dose radiotherapy concurrent with atezolizumab and chemotherapy as first-line treatment for extensive-stage small-cell lung cancer: 3-year follow-up of a multicenter, single-arm, phase 2 trial (MATCH)

Int J Radiat Oncol Biol Phys. 2025 Jul 1:S0360-3016(25)04508-0. doi: 10.1016/j.ijrobp.2025.06.3872. Online ahead of print.

Authors

Lin Zhou¹, Jianguo Sun², Conghua Xie³, Kai Kang¹, Zhuoran Yao⁴, Youling Gong¹, Meijuan Huang⁴, Hui Wang⁵, Lin Wu⁶, Zhiyong Yuan⁷, Nan Bi⁸, Min Fan⁹, Yaping Xu¹⁰, Yao Chen¹¹, You Lu¹²; MATCH study group

Collaborators

MATCH study group:
You Lu¹³, Lin Zhou¹³, Youling Gong¹³, Meijuan Huang¹³, Kai Kang¹³, Yan Zhang¹³, Yongmei Liu¹³, Jiang Zhu¹³, Bingwen Zou¹³, Min Yu¹³, Weigang Xiu¹³, Yanying Li¹³, Xuanwei Zhang¹³, Feifei Na¹³, Zhuoran Yao¹³, Jianxin Xue¹³, Ruizhan Tong¹³, Li Li¹³, Qi Lu¹³, Lang He¹⁴, Xi Lin¹⁵, Xiaojuan Zhou¹³, Yong Xu¹³, Jin Wang¹³, Feng Peng¹³, Yang Yu¹³, Lisha Xiang¹³, Shasha Zeng¹³, Ren Luo¹³, Yijun Wu¹³, Jialong Han¹³, Ou Peng¹³, Fangyun Yang¹³, Yuming Jia¹⁶, Ou Jiang¹⁷, Xingyuan Wang¹⁸, Xiaolin Lei¹⁹, Hui Wang²⁰, Lin Wu²⁰, Qianzhi Wang²⁰, Wenjuan Yang²⁰, Yi Kong²⁰, Min Fan²¹, Boyan Wang²¹, Yaping Xu²², Chenxue Jiang²², Jianguo Sun²³, Anmei Zhang²³, Conghua Xie²⁴, Jing Yu²⁴, Zhiyong Yuan²⁵, Yong Guan²⁵, Nan Bi²⁶, Lei Deng²⁶

Affiliations

¹ Division of Thoracic Tumor Multimodality Treatment, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China, 610041; Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China, 610041.
² Cancer Institute, Xinqiao Hospital, Army Medical University, Chongqing, China.
³ Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.
⁴ Division of Thoracic Tumor Multimodality Treatment, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China, 610041.
⁵ Department of Radiation Oncology, Hunan Cancer Hospital, Changsha, China.
⁶ Department of Thoracic Medicine, Hunan Cancer Hospital, Changsha, China.
⁷ Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
⁸ Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
⁹ Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
¹⁰ Department of Radiation Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
¹¹ Medical Affairs, Shanghai Roche Pharmaceuticals Ltd., Shanghai, China.
¹² Division of Thoracic Tumor Multimodality Treatment, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China, 610041; Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China, 610041. Electronic address: radyoulu@hotmail.com.
¹³ West China Hospital, Sichuan University.
¹⁴ Chengdu Fifth People's Hospital.
¹⁵ Mianzhu People's Hospital.
¹⁶ Yibin Second People's Hospital.
¹⁷ The Second People's Hospital of Neijiang.
¹⁸ Guang'an People's Hospital.
¹⁹ The Affiliated Hospital of Panzhihua University.
²⁰ Hunan Cancer Hospital.
²¹ Fudan University Shanghai Cancer Center.
²² Shanghai Pulmonary Hospital, Tongji University School of Medicine.
²³ Xinqiao Hospital, Army Medical University.
²⁴ Zhongnan Hospital of Wuhan University.
²⁵ Tianjin Medical University Cancer Institute and Hospital.
²⁶ Chinese Academy of Medical Sciences and Peking Union Medical College.

PMID: 40609842
DOI: 10.1016/j.ijrobp.2025.06.3872

Abstract

Purpose: Preclinical studies showed that low-dose radiotherapy (LDRT) may act synergistically with immunotherapy in small-cell lung cancer (SCLC); however, its role in the treatment of extensive-stage SCLC (ES-SCLC) remains unclear.

Methods and materials: This single-arm, multicenter, Simon's two-stage, phase II study enrolled treatment-naïve patients with ES-SCLC. Patients received four 21-day cycles of intravenous cisplatin (75 mg/m²) or carboplatin (area under the curve, 5 mg/mL/min), etoposide (100 mg/m²), and atezolizumab (1200 mg), with concurrent LDRT (15 Gy in 5 fractions [3 Gy/fraction]), followed by atezolizumab maintenance therapy until loss of clinical benefit, unacceptable toxicity, withdrawal of consent, or death. The primary endpoint was confirmed objective response rate (ORR). The secondary endpoints were progression-free survival (PFS) and overall survival (OS).

Results: Fifty-six eligible patients were enrolled between December 16, 2020, and March 30, 2022. The median follow-up was 36.1 months (interquartile range 30.9-38.7) at the cutoff date (June 30, 2024). The confirmed ORR was 87.5% (95% confidence interval [CI] 75.9-94.8). The median PFS and OS were 6.9 months (95% CI, 5.4-9.3) and 16.9 months (95% CI, 14.0-32.9), respectively. The PFS rates at 1 and 3 years were 27.3% and 20.7%, respectively, and the OS rates at 1 and 3 years were 69.6% and 35.1%. The median depth of tumor response (mDpR) among patients with confirmed objective response was 70.2%. The 3-year OS rates were 57.4% and 18.8% in patients above and below the mDpR, respectively (hazard ratio, 0.28; 95% CI, 0.13-0.60). The most common treatment-related grade 3-5 adverse events were decreased neutrophil count (60.7%) and decreased white blood cell count (58.9%).

Conclusions: These findings suggest that upfront LDRT concurrent with atezolizumab plus chemotherapy was effective and tolerable as first-line treatment for ES-SCLC, warranting further verification in randomized controlled trials.