Consolidative Stereotactic Radiotherapy for Oligo-Residual Advanced EGFR-Mutant NSCLC After First-Line Third-Generation EGFR-TKI Plus Chemotherapy

This national multicenter, randomized controlled clinical trial evaluates the safety and efficacy of consolidative stereotactic radiotherapy in patients with advanced EGFR-mutant non-small cell lung cancer who have oligo-residual disease after four cycles of first-line treatment with third-generation EGFR-TKI plus platinum-based pemetrexed chemotherapy. Eligible participants will be randomized 1:1 to continue third-generation EGFR-TKI plus pemetrexed maintenance therapy alone or to receive stereotactic radiotherapy to all oligo-residual lesions in addition to the same maintenance therapy. The primary endpoint is progression-free survival.

Inclusion Criteria: * Histologically confirmed non-small cell lung cancer. * Clinical stage IV disease according to the AJCC 9th edition. * Sensitizing EGFR mutation: EGFR exon 19 deletion or EGFR L858R. * Age 18-75 years. * Karnofsky Performance Status score ≥70. * Complete whole-body imaging assessment before initiation of first-line third-generation EGFR-TKI plus chemotherapy, with at least one evaluable lesion according to RECIST version 1.1. * No disease progression after completion of four cycles of first-line third-generation EGFR-TKI plus chemotherapy and no unresolved grade ≥3 nonhematologic toxicity. * Oligo-residual disease after four treatment cycles, with all residual lesions considered suitable for stereotactic radiotherapy by the investigator. * Written informed consent. Exclusion Criteria: * Double primary or multiple primary malignancies, except early skin cancer or cervical carcinoma in situ treated with curative intent and without recurrence or progression for at least five years. * Pregnancy or breastfeeding, or considered unsuitable by the investigator for PET/CT or brain MRI examination. * History of uncontrolled epilepsy, central nervous system disease, or psychiatric disorder that, in the investigator's judgment, may interfere with informed consent or participant compliance. * Residual lesions considered unsuitable for consolidative stereotactic radiotherapy after first-line third-generation EGFR-TKI plus chemotherapy.