Efficacy of osimertinib in EGFR-mutated non-small-cell lung cancer

Results from the LAURA trial, recently published on The New England Journal of Medicine, showed that a treatment with the EGFR tyrosine kinase inhibitor osimertinib significantly increases progression-free survival than placebo in patients with unresectable stage III EGFR-mutated non-small-cell lung cancer (NSCLC) with progression after chemotherapy.

The LAURA study is a phase III, double-blind, placebo-controlled trial where 216 patients with unresectable EGFR-mutated stage III NSCLC who had undergone chemoradiotherapy were randomly assigned to receive osimertinib or placebo until disease progression. Osimertinib is a third-generation EGFR tyrosine kinase inhibitor used as preferred first-line treatment for advanced EGFR-mutated NSCLC and is also approved for use in combination with platinum-based chemotherapy in this context. In addition, osimertinib is recommended as adjuvant treatment for resected stage IB–IIIA EGFR-mutated NSCLC; others EGFR tyrosine kinase inhibitor have shown preliminary efficacy in unresectable stage III EGFR-mutated NSCLC. In this study, median progression-free survival was 39.1 months with osimertinib versus 5.6 months with placebo; the percentage of patients who were alive and progression free at 12 months was 74% with osimertinib and 22% with placebo. Interim overall survival data showed 36-month overall survival among 84% of patients with osimertinib and 74% with placebo. The median duration of total treatment exposure was longer with osimertinib than placebo (24.0 months vs. 8.3 months), but the majority of adverse events reported with osimertinib were mild or moderate in severity and did not lead to treatment discontinuation; no new safety concerns emerged. As authors conclude, «Treatment with osimertinib resulted in significantly longer progression-free survival than placebo in patients with unresectable stage III EGFR-mutated NSCLC. Additional data and longer follow-up are needed on overall survival, central nervous system progression-free survival, safety, health-related quality of life and circulating tumor DNA; research on the efficacy and safety of treatment with EGFR tyrosine kinase inhibitors, either before or after chemoradiotherapy, would also be of interest in this patient group».