Mutation testing, treatment patterns, and outcomes in patients with unresectable stage III EGFR-mutated non-small cell lung cancer treated with chemoradiotherapy: Final analysis of a global real-world study

Abstract

Introduction: In the phase III LAURA study, osimertinib after definitive chemoradiotherapy (CRT) demonstrated a statistically significant, clinically meaningful progression-free survival (PFS) benefit over placebo in patients with unresectable stage III epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). Understanding real-world (rw) treatment patterns and clinical outcomes can help to measure the impact of new treatments. We report final results from a global, retrospective rw study of patients with unresectable stage III EGFR-mutated NSCLC treated with CRT. Materials and methods: Data were extracted from medical records of adults with unresectable stage III EGFR-mutated (Ex19del/L858R) NSCLC, diagnosed January 2016-December 2019, who received CRT as standard of care. The primary outcome was rwPFS. Secondary outcomes included mutation testing patterns and treatment patterns, rw time to next treatment or death (rwTTNTD) and overall survival (OS). Analyses are descriptive; time-to-event outcomes were estimated using Kaplan-Meier methods. Results: Data were included from 172 patients; 59 % of patients harbored Ex19del and 41 % L858R; 76 % received concurrent CRT and 24 % sequential CRT. Overall, 78 %, 18 %, 3 %, and 1 % of patients received CRT alone, CRT plus durvalumab, CRT plus an EGFR-tyrosine kinase inhibitor (TKI) and CRT plus pembrolizumab, respectively, as their first treatment. Of patients who received subsequent treatment (n = 115), most received EGFR-TKIs (75 %; n = 86/115). In patients who received CRT alone as first treatment, median (95 % confidence interval) rwPFS, rwTTNTD, and OS were 6.7 (6.0-9.0), 11.4 (9.0-14.4), and 68.6 (60.9-not evaluable) months, respectively. Conclusion: In this rw study in patients with unresectable stage III EGFR-mutated NSCLC, CRT alone was the most common first treatment and EGFR-TKIs were the most common first subsequent treatment. OS was substantial despite relatively short rwPFS, which may be attributed to subsequent EGFR-TKIs. The findings highlight the unmet need for alternative treatments in this setting.