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

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.

• Authors: Xiao-Shan Wang, Yi-Feng Bai, Vivek Verma, Rui-Lian Yu, Wei Tian, Rui Ao, Ying Deng, Xue-Qiang Zhu, Hao Liu, Hai-Xia Pan, Lan Yang, Han-Song Bai, Xing Luo, Yan Guo, Ming-Xiu Zhou, Yue-Mei Sun, Zi-Can Zhang, Si-Min Li, Xue Cheng, Bang-Xian Tan, Liang-Fu Han, Ying-Yi Liu, Kai Zhang, Fan-Xin Zeng, Lin Jia, Xin-Bao Hao, You-Yu Wang, Gang Feng, Ke Xie, You Lu, Ming Zeng
• Journal: Journal of the National Cancer Institute (J Natl Cancer Inst) Vol. 115 Issue 6 Pg. 742-748 (06 08 2023) ISSN: 1460-2105 [Electronic] United States
• PMID: 35094066 (Publication Type: Randomized Controlled Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2022. Published by Oxford University Press.

Chemical References

• Tyrosine Protein Kinase Inhibitors
• Protein Kinase Inhibitors
• ErbB Receptors
• EGFR protein, human

Topics

• Humans
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics, radiotherapy)
• Tyrosine Protein Kinase Inhibitors
• Lung Neoplasms (drug therapy, genetics, radiotherapy)
• Protein Kinase Inhibitors (adverse effects)
• ErbB Receptors (genetics)
• Mutation