Surgical Intervention Following EGFR TKI Therapy Shows Potential to Extend Progression-Free Survival in Metastatic Non-Small Cell Lung Cancer

A recent Phase II clinical trial conducted by the National Taiwan University Hospital has provided encouraging evidence that surgical removal of the primary tumor after initial EGFR TKI therapy may help prolong disease control in patients with metastatic EGFR-mutated non-small cell lung cancer (NSCLC). Presented at the 2025 World Conference on Lung Cancer by the International Association for the Study of Lung Cancer, the study explored how combining targeted therapy with surgery could impact patient outcomes.

The trial included both oligometastatic and polymetastatic patients and was the first to evaluate the effects of surgical resection following targeted therapy in this patient population. Patients received 12 weeks of afatinib, an EGFR TKI, after which they were randomized into two groups: one continued with medication alone, while the other underwent surgery to resect the primary tumor. Surgeons also had the discretion to administer radiotherapy for non-pulmonary metastases.

Lead researcher Dr. Pei-Hsing Chen explained that the purpose of surgery is not curative but to serve as part of a strategy to delay the development of drug resistance and improve progression-free survival (PFS). The study's early results indicate that this approach can significantly extend the time before disease progression, with a hazard ratio for progression of 0.48, meaning nearly half the risk compared to standard therapy alone.

Key findings from the trial include:

• An improved two-year PFS in the surgical group.
• Major pathologic response (MPR) observed in approximately 29.4% of resected tumors, with 5.9% achieving pathological complete response.
• The Exon 19 deletion subgroup showed higher MPR rates, while the L858R mutation subgroup experienced a more favorable PFS hazard ratio.
• Molecular analysis of postoperative tissue revealed TP53 mutations in about 36.6% of cases, with co-mutations present in half of the samples; these genetic factors showed trends toward poorer outcomes, though not statistically significant.

Dr. Chen emphasized that the surgical approach not only holds promise for prolonging disease control but also provides valuable tissue samples for molecular studies, which could inform future targeted treatments. Overall, these innovative findings highlight the potential benefits of integrating surgery into the treatment paradigm for selected metastatic NSCLC patients advancing after EGFR TKI therapy.

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