Efficacy and acquired resistance for EGFR-TKI plus thoracic SBRT in patients with advanced EGFR-mutant non-small-cell lung cancer: a propensity-matched retrospective study.
BACKGROUND
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.


METHODS
Patients 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.


RESULTS
Three 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.


CONCLUSION
Real 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.
['Wang|Xia|X|', 'Zeng|Zhimin|Z|', 'Cai|Jing|J|', 'Xu|Peng|P|', 'Liang|Pingan|P|', 'Luo|Yuxi|Y|', 'Liu|Anwen|A|http://orcid.org/0000-0001-5279-1068']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D000970:Antineoplastic Agents D002289:Carcinoma, Non-Small-Cell Lung D059248:Chemoradiotherapy D004247:DNA D019008:Drug Resistance, Neoplasm D066246:ErbB Receptors D005260:Female D059014:High-Throughput Nucleotide Sequencing D006801:Humans D008175:Lung Neoplasms D008297:Male D008875:Middle Aged D009154:Mutation D000077982:Progression-Free Survival D057216:Propensity Score D047428:Protein Kinase Inhibitors D016634:Radiosurgery D012189:Retrospective Studies D055815:Young Adult
Stereotactic body radiation therapy Propensity score matching Acquired resistance mechanism Epidermal growth factor receptor tyrosine kinase inhibitors Non-small-cell lung cancer