P89.05 Management of Patients with EGFR and ALK-Mutated Advanced Non-Small Cell Lung Cancer Post-TKI Therapy – A Real-World Survival Analysis

Abstract

Targeted therapy with tyrosine kinase inhibitors (TKIs) is the preferred first-line therapy for advanced non-small cell lung cancer (NSCLC) with actionable mutations. It is unknown which treatment strategy is most efficacious post-TKI progression. Studies have demonstrated minimal activity with single-agent immune checkpoint inhibitors (ICIs) and most combination chemoimmunotherapy (CIO) trials have excluded EGFR and ALK-mutated patients. We performed a real-world analysis to evaluate time to next treatment (TTNT) and overall survival (OS) for patients with EGFR and ALK-mutated NSCLC post-TKI progression. The study included patients with EGFR and ALK-mutated NSCLC in the Flatiron Health nationwide electronic health record-derived de-identified database who initiated chemotherapy (C), CIO, immunotherapy (IO), or C with VEGF inhibition (CV) post-progression after initial treatment with one or more TKIs between 2011-2018, with follow-up through June 2019. We excluded patients with over 90 days between advanced diagnosis date and next visit to ensure patients were actively involved in care, and required initiation of post-TKI therapy at least 6 months before end of follow-up. TTNT and OS were compared for the four post-TKI therapy categories using Kaplan-Meier curves and multivariable Cox proportional hazards models. Models were adjusted for smoking (history/none), gender, age at post-TKI therapy, year of post-TKI therapy, time on TKI therapy, number of initial TKI therapies, and ECOG PS at time of TKI failure. This study included 480 patients with EGFR and 86 patients with ALK-mutated NSCLC. In adjusted analyses for TTNT, patients with EGFR-mutated tumors who received CIO and CV demonstrated improvements in TTNT with HRs of 0.46 (95% CI 0.30-0.70, p<0.001) and 0.74 (95% CI 0.57-0.96, p=0.02) relative to C, respectively. No statistically significant difference in TTNT between IO and C was detected. Results were similar among ALK-mutated patients, although not statistically significant. In adjusted analyses for TTNT, patients receiving CIO and CV had HRs of 0.40 (95% CI 0.15-1.06, p=0.06) and 0.52 (95% CI 0.25-1.06, p=0.07) relative to C, respectively. In adjusted analyses for OS, the only statistically significant finding was for CIO vs. C (HR 0.55, 95% CI 0.31-0.98, p=0.04) among patients with EGFR-mutated tumors. Patients with EGFR and ALK-mutated advanced NSCLC demonstrate a TTNT benefit from combined CIO and C with VEGF inhibition post-TKI progression in the real-world. Ongoing and future clinical trials are needed to provide prospective evidence for the management of combination therapies in EGFR and ALK-mutated NSCLC patients who have exhausted TKI options.