Local Consolidation Therapy (LCT) After First Line Tyrosine Kinase Inhibitor (TKI) for Patients With EGFR Mutant Metastatic Non–small-cell Lung Cancer (NSCLC)

Introduction Although most NSCLC patients with sensitizing epidermal growth factor receptor (EGFR) mutations have an impressive initial response, the vast majority has residual disease and develops acquired resistance after 9 to 14 months of EGFR tyrosine kinase (TKI) therapy. We recently reported a phase II trial showing that, for patients with molecularly unselected oligometastatic NSCLC who did not progress after first-line systemic therapy, local consolidation therapy (LCT) with surgery or radiation improved progression-free survival (PFS), compared with maintenance therapy alone. Herein, we report a retrospective analysis of LCT after TKI in patients with metastatic EGFR mutant NSCLC. Patients and Methods We identified patients with metastatic EGFR mutant NSCLC treated with TKI plus LCT or with TKI alone in the MD Anderson GEMINI (Genomic Marker-Guided Therapy Initiative) database and in our recently published LCT trial. PFS was compared between LCT plus TKI and TKI only treated patients using the log-rank test. Results We identified 129 patients with EGFR mutant NSCLC who were treated with first-line TKI and 12 that were treated with TKI followed by LCT. Among the 12 patients treated with TKI plus LCT, 8 patients had oligometastatic disease (defined as ≤ 3 metastases), and 4 patients had > 3 metastases. LCT regimens were hypofractionated radiotherapy or stereotactic ablative body radiotherapy for 11 patients and surgery for 1 patient. TKI followed by LCT resulted in a significantly longer PFS (36 months) compared with TKI alone (PFS, 14 months; log-rank P = .0024). Conclusions Our data suggests that first-line TKI plus LCT is a promising therapeutic strategy for patients with EGFR mutant NSCLC that merits further investigation.