Randomized Trial of First-Line Tyrosine Kinase Inhibitor With or Without Radiotherapy for Synchronous Oligometastatic EGFR-Mutated Non-Small Cell Lung Cancer

• Published in: JNCI : Journal of the National Cancer Institute Vol. 115; no. 6; pp. 742 - 748
• Main Authors: Wang, Xiao-Shan, Bai, Yi-Feng, Verma, Vivek, Yu, Rui-Lian, Tian, Wei, Ao, Rui, Deng, Ying, Zhu, Xue-Qiang, Liu, Hao, Pan, Hai-Xia, Yang, Lan, Bai, Han-Song, Luo, Xing, Guo, Yan, Zhou, Ming-Xiu, Sun, Yue-Mei, Zhang, Zi-Can, Li, Si-Min, Cheng, Xue, Tan, Bang-Xian, Han, Liang-Fu, Liu, Ying-Yi, Zhang, Kai, Zeng, Fan-Xin, Jia, Lin, Hao, Xin-Bao, Wang, You-Yu, Feng, Gang, Xie, Ke, Lu, You, Zeng, Ming
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 08.06.2023; Oxford Publishing Limited (England)
• Subjects: Adenocarcinoma; Biopsy; Brain cancer; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - radiotherapy; Epidermal growth factor receptors; ErbB Receptors - genetics; Fractions; Gefitinib; Growth factors; Humans; Inhibitor drugs; Kinases; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - radiotherapy; Metastases; Metastasis; Mutation; Next-generation sequencing; Non-small cell lung carcinoma; Pneumonitis; Protein Kinase Inhibitors - adverse effects; Radiation therapy; Randomization; Sequences; Small cell lung carcinoma; Statistical analysis; Statistical tests; Survival; Targeted cancer therapy; Tumors; Tyrosine; Tyrosine Kinase Inhibitors
• ISSN: 0027-8874; 1460-2105; 1460-2105
• DOI: 10.1093/jnci/djac015

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 epidermal growth factor receptor (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 upfront RT vs no RT; we now report the prespecified 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 and 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 with 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 with RT. Treatment yielded no grade 5 events and a 6% rate of symptomatic grade 3-4 pneumonitis in the TKI with RT arm. Based on the efficacy results of this prespecified interim analysis, the ethics committee recommended premature cessation of this trial. Conclusions As compared with a first-line TKI alone, addition of upfront local therapy using RT statistically significantly improved PFS and OS for EGFR-mutated NSCLC.