Researchers of a randomized phase 2 trial asked whether resecting the primary thoracic tumor after 12 weeks of afatinib could prolong disease control in EGFR-mutant metastatic non-small cell lung cancer. Patients either continued afatinib or underwent primary tumor resection (± radiotherapy) as local consolidation. The aim was non-curative—debulking disease, targeting resistant subclones, delaying drug resistance, and obtaining tissue for analysis. Notably, this is the first trial to test primary tumor resection with an EGFR tyrosine kinase inhibitor (TKI) across both oligometastatic and polymetastatic settings.
Early efficacy signals favored surgery: the hazard ratio (HR) for progression was 0.48 (95% confidence interval, 0.25–0.93; P = .031), with immature data. Major pathologic response (MPR) occurred in 29.4% of resected cases, with 5.9% achieving pathologic complete response, though MPR has not yet correlated with survival outcomes. Next-generation sequencing of postoperative samples (n = 30) revealed TP53 mutations in 36.6% and co-mutations in 50%; associated HRs (1.4 for TP53, 1.7 for co-mutations) did not reach statistical significance. Ongoing follow-up will clarify durability, refine subgroup selection, and determine whether pathologic metrics translate into longer-term clinical benefit.
Reference: The ASCO Post Staff. Surgical Resection With EGFR TKI Demonstrates Promising PFS in EGFR-Mutant NSCLC. The ASCO Post. Published September 15, 2025. Accessed September 26, 2025. https://ascopost.com/news/september-2025/surgical-resection-with-egfr-tki-demonstrates-promising-pfs-in-egfr-mutant-nsclc/
Link: https://ascopost.com/news/september-2025/surgical-resection-with-egfr-tki-demonstrates-promising-pfs-in-egfr-mutant-nsclc/
