Clinical outcome of EGFR-mutant NSCLC patients continuing TKIs beyond progression in combination with local ablative radiotherapy.

Abstract

e20662 Background: Continuation of EGFR TKIs with or without local ablative treatments in patients with metastatic EGFR-mutant NSCLC experiencing disease progression under TKIs is feasible and may be associated with improved outcomes. Methods: The retrospective analysis includes 130 patients with advanced EGFR-mutant NSCLC experiencing RECIST disease progression under first-line gefitinib or afatinib, treated in 3 Italian centers between 2011 and 2016. In group 1 (n = 99, 76.2%) patients stopped TKI treatment at first RECIST-confirmed progression while in group 2 (n = 31, 23.8%) TKIs were continued and sites of progression were irradiated. The primary endpoint was overall survival (OS). Progression-free survival (PFS) and time to treatment failure (TTF) were calculated from the start of first-line TKIs. Kaplan-Meier method, the log-rank test and multivariate Cox regression models were used to estimate outcome endpoints. Median follow-up time was 40 months. Results: Median OS, PFS and TTF in the whole cohort were 22.4, 11.1 and 13.0 months, respectively. The two groups resulted well balanced in terms of patients’ characteristics and TKI administered. Median OS was significantly longer in group 2 (37.3 vs 15.6 months; HR 0.33; 95%CI 0.22-0.50; p < 0.0001), as well as median PFS (13.8 vs 8.9 months; HR 0.60; 95%CI 0.42-0.86; p = 0.01) and median TTF (29.3 vs 10.4 months; HR 0.30; 95%CI 0.21-0.44; p < 0.0001). Ten out of 31 (32.3%) patients underwent radiotherapy in ≥2 sites of progressive disease; the most frequently irradiated site was bone (n = 16), followed by brain (n = 9), lung (n = 8) and lymph nodes (n = 6). On multivariate analysis including age, sex, smoking history, mutant exon, presence of brain metastases, TKI administered and treatment strategy at progression, only TKI continuation with radiotherapy was independently associated with all outcome endpoints (OS: p = 0.0007, PFS: p = 0.004; TTF: p < 0.0001). Conclusions: In EGFR-mutant NSCLC progressing under first-line TKIs continuation of TKI in association with local ablative radiotherapy is associated with prolonged OS, PFS and TTF. Whether the improved outcome is a result of treatment strategy or more indolent disease remains unclear.