Efficacy and acquired resistance for EGFR-TKI plus thoracic SBRT in patients with advanced EGFR-mutant non\u2013small-cell\u2002lung\u2002cancer: a propensity-matched retrospective study

Xia Wang,Anwen Liu,Yuxi Luo,Pingan Liang,Peng Xu,Jing Cai,Zhimin Zeng

doi:10.1186/s12885-021-08228-2

Abstract

BackgroundThis retrospective study aimed to evaluate the efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) with stereotactic body radiation therapy (SBRT) and to elucidate potential mechanisms of acquired resistance.MethodsPatients with advanced NSCLC harboring positive EGFR mutations after initial TKI therapy for at least 8 weeks were eligible for SBRT between August 2016 and August 2019. Eligible patients were treated with thoracic SBRT, and TKI was continued after SBRT until it was considered ineffective. The control group was treated with TKIs monotherapy. Propensity score matching (PSM, ratio of 1:2) was used to account for differences in baseline characteristics. Overall survival (OS), progression-free survival (PFS), treatment safety and resistance mechanisms were evaluated.ResultsThree hundred eight patients were included in the study population. Among them, 262 patients received TKIs alone, and 46 patients received TKIs with SBRT. Baseline characteristics were not significantly different between the two cohorts after PSM. The median PFS was 19.4 months in the TKIs +SBRT group compared to 13.7 months in the TKIs group (p = 0.034). An influence on OS has not yet been shown (p = 0.557). Of the 135 patients evaluated after PSM, 28 and 71 patients in the TKIs and TKIs +SBRT cohorts, respectively, had plasma cell-free DNA (cfDNA) next-generation sequencing (NGS) performed at baseline and disease progression. In the TKIs +SBRT cohort, the NGS results showed that T790M mutations were detected in 64.3% (18/28) of patients. Patients in the TKIs cohort exhibited fewer T790M-positive mutations (40.8%, p = 0.035) compared to patients in the TKIs +SBRT cohort.ConclusionReal world data prove that TKIs plus thoracic SBRT significantly extend PFS with tolerable toxicity. The mutation ratio of T790M was increased in the TKIs +SBRT group compared to the TKIs only group. Further randomized studies are warranted.

Highlights

This retrospective study aimed to evaluate the efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) with stereotactic body radiation therapy (SBRT) and to elucidate potential mechanisms of acquired resistance
Real world data prove that TKIs plus thoracic SBRT significantly extend progression-free survival (PFS) with tolerable toxicity
The mutation ratio of T790M was increased in the TKIs +SBRT group compared to the TKIs only group

Summary

Introduction

This retrospective study aimed to evaluate the efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) with stereotactic body radiation therapy (SBRT) and to elucidate potential mechanisms of acquired resistance. A number of studies [3,4,5,6] have confirmed that patients with advanced NSCLC with EGFR mutations can gain survival benefits from multiple generation tyrosine kinase inhibitors (TKIs), such as erlotinib, gefitinib or afatinib, and the efficacy is better than systemic chemotherapy. Several small prospective trials have shown that LCT, like surgery or stereotactic body radiation therapy (SBRT), can prolong PFS in patients with NSCLC and delay drug resistance in EGFR-TKIs when patients develop oligoprogression, oligometastases or oligopersistence [11, 12]. The lung was the most common site of initial progression, and 45% of patients progressed in primary sites (with or without concurrent metastatic sites) [14]

Methods

Results

Discussion

Conclusion