Xiao-Shan Wang1, Yi-Feng Bai1, Vivek Verma2, Rui-Lian Yu1, Wei Tian1, Rui Ao1, Ying Deng1, Jian-Ling Xia1, Xue-Qiang Zhu1, Hao Liu1, Hai-Xia Pan1, Lan Yang1, Yang-Ke He1, Han-Song Bai3, Xing Luo3, Yan Guo3, Ming-Xiu Zhou3, Yue-Mei Sun4, Zi-Can Zhang4, Si-Min Li3,5, Xue Cheng3, Bang-Xian Tan3, Liang-Fu Han6, Ying-Yi Liu7, Kai Zhang8, Fan-Xin Zeng9, Lin Jia10, Xin-Bao Hao11, You-Yu Wang1, Gang Feng1, Ke Xie1, You Lu12, Ming Zeng1. 1. Cancer Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China. 2. Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, NE, USA. 3. School of Medicine, University of Electronic Science and Technology of China, Chengdu, China. 4. Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan Province, China. 5. Southwest Medical University, Luzhou City, Sichuan Province, China. 6. Boao Evergrande International Hospital, Qionghai, Hainan Province, China. 7. Cancer Center, Sichuan Friendship Hospital, Chengdu, Sichuan Province, China. 8. Cancer Center, Ziyang People's Hospital, Ziyang, Sichuan Province, China. 9. Dazhou Central Hospital, Dazhou, Sichuan Province, China. 10. Third Hospital of Mianyang (Sichuan Mental Health Center), Mianyang, Sichuan Province, China. 11. Cancer Center, First Affiliated Hospital of Hainan Medical College, National Drug Clinical Trial Institute, Haikou, Hainan Province, China. 12. Cancer Center, West China Hospital, Chengdu, Sichuan Province, China.
Abstract
BACKGROUND: Adding radiotherapy (RT) to systemic therapy improves progression-free survival (PFS) and overall survival (OS) in oligometastatic non-small cell lung cancer (NSCLC). Whether these findings translate to EGFR-mutated NSCLC remains unknown. The SINDAS trial (NCT02893332) evaluated first-line tyrosine kinase inhibitor (TKI) therapy for EGFR-mutated synchronous oligometastatic NSCLC, and randomized to up-front RT vs. no RT; we now report the pre-specified interim analysis at 68% accrual. METHODS: Inclusion criteria were biopsy-proven EGFR-mutated adenocarcinoma (per amplification refractory mutation system or next generation sequencing), with synchronous (newly-diagnosed, treatment-naïve) oligometastatic (≤5 metastases; ≤2 lesions in any one organ) NSCLC without brain metastases. All patients received a first-generation TKI (gefitinib, erlotinib, or icotinib), and randomization was between no RT vs. RT (25-40 Gy in 5 fractions depending on tumor size/location) to all metastases and the primary tumor/involved regional lymphatics. The primary endpoint (intention-to-treat) was PFS. Secondary endpoints included OS and toxicities. All statistical tests were 2-sided. RESULTS: A total of 133 patients (n = 65 TKI only, n = 68 TKI+RT) were enrolled (2016-2019). The median follow-up was 23.6 months. The respective median PFS was 12.5 months vs. 20.2 months (p < .001), and the median OS was 17.4 months vs. 25.5 months (p < .001) for TKI only vs TKI+RT. Treatment yielded no grade 5 events and a 6% rate of symptomatic grade 3-4 pneumonitis in the TKI+RT arm. Based on the efficacy results of this pre-specified interim analysis, the ethics committee recommended premature cessation of this trial. CONCLUSIONS: As compared to a first-line TKI alone, addition of up-front local therapy using RT statistically significantly improved PFS and OS for EGFR-mutated NSCLC.
BACKGROUND: Adding radiotherapy (RT) to systemic therapy improves progression-free survival (PFS) and overall survival (OS) in oligometastatic non-small cell lung cancer (NSCLC). Whether these findings translate to EGFR-mutated NSCLC remains unknown. The SINDAS trial (NCT02893332) evaluated first-line tyrosine kinase inhibitor (TKI) therapy for EGFR-mutated synchronous oligometastatic NSCLC, and randomized to up-front RT vs. no RT; we now report the pre-specified interim analysis at 68% accrual. METHODS: Inclusion criteria were biopsy-proven EGFR-mutated adenocarcinoma (per amplification refractory mutation system or next generation sequencing), with synchronous (newly-diagnosed, treatment-naïve) oligometastatic (≤5 metastases; ≤2 lesions in any one organ) NSCLC without brain metastases. All patients received a first-generation TKI (gefitinib, erlotinib, or icotinib), and randomization was between no RT vs. RT (25-40 Gy in 5 fractions depending on tumor size/location) to all metastases and the primary tumor/involved regional lymphatics. The primary endpoint (intention-to-treat) was PFS. Secondary endpoints included OS and toxicities. All statistical tests were 2-sided. RESULTS: A total of 133 patients (n = 65 TKI only, n = 68 TKI+RT) were enrolled (2016-2019). The median follow-up was 23.6 months. The respective median PFS was 12.5 months vs. 20.2 months (p < .001), and the median OS was 17.4 months vs. 25.5 months (p < .001) for TKI only vs TKI+RT. Treatment yielded no grade 5 events and a 6% rate of symptomatic grade 3-4 pneumonitis in the TKI+RT arm. Based on the efficacy results of this pre-specified interim analysis, the ethics committee recommended premature cessation of this trial. CONCLUSIONS: As compared to a first-line TKI alone, addition of up-front local therapy using RT statistically significantly improved PFS and OS for EGFR-mutated NSCLC.
Authors: Alexander Yaney; Andrew Stevens; Paul Monk; Douglas Martin; Dayssy A Diaz; Shang-Jui Wang Journal: Front Oncol Date: 2022-06-08 Impact factor: 5.738
Authors: Zhengfei Zhu; Jianjiao Ni; Xuwei Cai; Shengfa Su; Hongqing Zhuang; Zhenzhou Yang; Ming Chen; Shenglin Ma; Conghua Xie; Yaping Xu; Jiancheng Li; Hong Ge; Anwen Liu; Lujun Zhao; Chuangzhou Rao; Congying Xie; Nan Bi; Zhouguang Hui; Guangying Zhu; Zhiyong Yuan; Jun Wang; Lina Zhao; Wei Zhou; Chai Hong Rim; Arturo Navarro-Martin; Ben G L Vanneste; Dirk De Ruysscher; J Isabelle Choi; Jacek Jassem; Joe Y Chang; Lucyna Kepka; Lukas Käsmann; Michael T Milano; Paul Van Houtte; Rafal Suwinski; Alberto Traverso; Hiroshi Doi; Yang-Gun Suh; Georges Noël; Natsuo Tomita; Roman O Kowalchuk; Terence T Sio; Baosheng Li; Bing Lu; Xiaolong Fu Journal: Transl Lung Cancer Res Date: 2022-09