Resection of the primary thoracic tumor after EGFR tyrosine kinase inhibition demonstrated the ability to prolong disease control in patients with EGFR-mutant metastatic non–small cell lung cancer (NSCLC), according to findings from a randomized phase II trial presented at the International Association for the Study of Lung Cancer (IASLC) 2025 World Conference on Lung Cancer (WCLC; Abstract OA07.04).
“Our study explores whether targeting residual disease through surgery can extend the benefits of EGFR tyrosine kinase inhibition beyond standard monotherapy. The purpose of surgery is not curative, but rather to serve as part of a combination therapy to prolong the interval before drug resistance develops,” said presenting author Pei-Hsing Chen, MD, of National Taiwan University Hospital, Taipei City, Taiwan. “The early results suggest this approach may improve progression-free survival while providing important tissue for molecular analysis.”
Background and Study Methods
The study authors hypothesized that surgical resection of the primary tumor, through targeting resistant subclones or by reducing the overall tumor burden, could prolong the duration of disease control in patients with EGFR-mutant NSCLC to try to improve outcomes beyond EGFR tyrosine kinase inhibition alone.
They conducted a two-arm phase II trial of patients with oligometastatic and polymetastatic EGFR-mutant advanced NSCLC, who were randomly assigned to continue afatinib after 12 prior weeks of afatinib treatment, or to undergo primary tumor resection for locoregional control with or without radiotherapy. They noted that this was the first trial to evaluate primary tumor resection as local consolidation therapy with EGFR tyrosine kinase inhibition in both oligometastatic and polymetastatic NSCLC.
Key Study Findings
The hazard ratio for progression was 0.48 (95% confidence interval [CI] = 0.25–0.93; P = .031); however, the data are still immature.
Major pathologic responses were reported in 29.4% of patients, with pathologic complete responses seen in 5.9%. Major pathologic response has not yet correlated with improved survival.
Patients with EGFR exon 19 deletions in the surgical arm had higher major pathologic response rates compared with patients with EGFR L858R mutations, but a lower hazard ratio for progression-free survival was seen in patients with L858R mutations than in those with exon 19 deletions.
“Early progression-free survival results are promising and the surgical approach provides access to postoperative pathologic and molecular data, offering new insights for future subgroup selection,” Dr. Chen reported.
Next-generation sequencing of postoperative tissue (n = 30) showed TP53 mutations in 36.6% of patients and co-mutations in 50%. The hazard ratio for TP53 mutations was 1.4 and 1.7 for co-mutations, but these results were not statistically significant.
Continued follow-up is necessary, and long-term outcomes are still pending for this study.
Disclosure: For full disclosures of the study authors, visit abstractsonline.com.
