First-Line Integration of Local Ablative Therapy With EGFR Tyrosine Kinase Inhibitors in Advanced EGFR+ NSCLC: A...

Systemic intensification strategies improve outcomes in advanced EGFR-mutated NSCLC but increase toxicity. Integrating local ablative therapy (LAT) with first-line EGFR tyrosine kinase inhibitor (TKI) monotherapy represents an alternative approach to enhance disease control while preserving long-term tolerability.

MEDLINE, Embase, and Elicit were searched to December 2025. The protocol was registered in PROSPERO (CRD420251244650). Randomized and nonrandomized comparative studies evaluating EGFR TKI with or without LAT integrated into first-line treatment, either upfront or as consolidative therapy, were included in quantitative meta-analyses. Single-arm and noncomparative studies were analyzed descriptively. Hazard ratios (HRs) were pooled using random-effects models. Prespecified subgroup analyses explored disease burden, LAT timing, study design (prospective versus retrospective), LAT site, and TKI generation.

A total of 31 studies met the inclusion criteria, including 24 comparative studies (six randomized, two prospective nonrandomized, and 16 retrospective). LAT integration significantly improved progression-free survival (HR = 0.45, 95% confidence interval: 0.37-0.55) and overall survival (HR = 0.52, 95% confidence interval: 0.40-0.67) versus EGFR TKI alone. Benefits were consistent across oligometastatic and unselected populations, upfront and consolidative strategies, LAT sites (primary tumor with or without metastatic sites), TKI generations, and prospective and retrospective studies. Radiotherapy-related toxicities, particularly pneumonitis, were more frequent with LAT, but grade more than or equal to 3 events were uncommon and no unexpected safety signals emerged.

Across a heterogeneous evidence base, integrating LAT into first-line EGFR TKI therapy is associated with improved progression-free survival and overall survival with acceptable toxicity. These findings support further prospective investigation to better define patient selection, optimal timing, and integration with contemporary systemic combination strategies.