Overview

• At WCLC 2025, COMPEL reported a significant PFS benefit for osimertinib plus platinum–pemetrexed versus placebo plus chemotherapy after non‑CNS progression on first‑line osimertinib (8.4 vs 4.4 months; HR 0.43).
• Overall survival favored the combination (15.9 vs 9.8 months; HR 0.71), though the confidence interval crossed 1, and OS data were reported as immature.
• In evaluable subgroups, non‑CNS PFS improved and CNS control signals were favorable for the combination, with longer CNS PFS in patients without baseline brain metastases, though CNS data were early.
• The safety profile was consistent with known toxicities, with higher rates of grade ≥3 adverse events on the combination (63% vs 46%) and similar fatal AE rates (one in each arm).
• The global, double‑blind phase 3 trial randomized 98 patients 1:1 and was presented in Barcelona, with investigators noting alignment with FLAURA2 results that support osimertinib plus chemotherapy in the first‑line setting.