Radiotherapy combined with third-generation EGFR tyrosine kinase inhibitor in first-line treatment of advanced oligometastatic non-small cell lung cancer: a single-center, retrospective study.

[BACKGROUND] Third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are the standard first-line therapy for advanced EGFR-mutant non-small cell lung cancer (NSCLC). However, disease progression remains inevitable, particularly in the oligometastatic setting. We hypothesized that local radiotherapy (RT) could alter the disease course by eradicating resistant clones. Therefore, this study aimed to evaluate the efficacy of RT combined with a third-generation EGFR-TKI as first-line therapy for advanced oligometastatic NSCLC.

[METHODS] We retrospectively analyzed EGFR-mutant advanced oligometastatic NSCLC patients treated with third-generation EGFR-TKI at Zhejiang Cancer Hospital. Patients were stratified into TKI only group and TKI + RT group. Efficacy and safety were compared across groups.

[RESULTS] From March 2021 to September 2023, a total of 260 patients were enrolled, including 143 received TKI only group and 117 received TKI + RT group. With the median follow-up of 26.2 months, the median progression-free survival (PFS) was 20.6 and 26.0 months (P=0.18), and the median overall survival (OS) was 45.5 and 52.2 months (P=0.98) for TKI only and TKI + RT group respectively. For the subgroup of delivered biologically effective dose with an α/β ratio of 10 Gy (BED), BED ≥50 Gy group achieved significantly better median PFS than the TKI only group (32.1 20.6 months; P=0.02), while BED <50 Gy group showed no significant improvement compared with TKI only group (22.1 20.6 months, P=0.61). The median OS had no significant differences for BED ≥50 Gy TKI only (P=0.26) and BED <50 Gy TKI only (P=0.72). The median PFS in patients with brain metastases was significantly improved with RT (BED ≥50 Gy) (37.9 17.3 months, P=0.02). Multivariate analysis identified female, N0-2 stage, non-smoking, 1-2 metastatic lesions, and RT (BED ≥50 Gy) as independent favorable prognostic factors for PFS. Subgroup analysis confirmed significantly improved PFS in patients with brain metastases. RT-related adverse events (AEs) (radiation pneumonitis, esophagitis, and cerebral edema) were all grade ≤2.

[CONCLUSIONS] RT (BED ≥50 Gy) combined with third-generation EGFR-TKI therapy improved PFS with favorable safety in EGFR-mutant advanced oligometastatic NSCLC.