Local consolidation therapy (LCT) after first line tyrosine kinase inhibitor (TKI) for patients with EGFR mutant metastatic non-small cell lung cancer (NSCLC).

Abstract

e20654 Background: Although most NSCLC patients with sensitizing EGFR mutations (L858R, Exon 19 deletion) have an impressive initial response, the vast majority develop acquired resistance after 9-14 months of EGFR TKI therapy. Clearly, more effective strategies to prevent resistance emergence are needed. We recently reported a randomized phase 2 trial that showed that LCT with surgery or radiation, for molecularly unselected patients with oligometastatic NSCLC who did not progress after initial systemic therapy, improved progression-free survival (PFS) compared to maintenance therapy alone (Gomez, et al., 2016). Herein, we aim to determine the outcomes of LCT after first line TKI in patients with metastatic EGFR mutant NSCLC. Methods: This is a post-hoc analysis of our recently published phase 2 clinical trial and a retrospective review of MD Anderson Cancer Center GEMINI database. Eligible patients had metastatic EGFR mutant NSCLC, had first line TKI without progression followed by LCT with surgery or radiation. Results:In GEMINI database, 129 EGFR (L858R/Exon 19 deletion) mutant NSCLC patients were treated with first line TKI (erlotinib, gefitinib or afatinib) and 12 were treated with TKI followed by LCT (3 treated within our published clinical trial and 9 at the discretion of their physician). 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 one patient. Patients treated with TKI followed by LCT had a significantly longer PFS (36 months) compared to patients treated with first line TKI alone (PFS 14 months, p = 0.0024, log-rank). Conclusions:Our retrospective data suggests that first line TKI plus LCT is a promising therapeutic strategy that led to a significant outcome improvement for patients with EGFR mutant NSCLC. A multicenter phase 2 clinical trial comparing TKI plus LCT to TKI alone is planned.