Overview

• FLAURA2 reported a statistically significant overall-survival benefit for first-line osimertinib plus chemotherapy versus monotherapy (HR 0.77; median OS 47.5 vs 37.6 months).
• COMPEL showed that continuing osimertinib with platinum–pemetrexed after non‑CNS progression on first‑line osimertinib improved progression-free survival (HR 0.43; 8.4 vs 4.4 months) and yielded longer median overall survival (15.9 vs 9.8 months).
• HARMONi found ivonescimab plus carboplatin/pemetrexed after third‑generation EGFR TKI failure significantly prolonged PFS (HR 0.52; 6.8 vs 4.4 months) with a positive OS trend (HR 0.79, P=0.057).
• ACROSS 2 showed that adding chemotherapy to aumolertinib in patients with tumor suppressor co‑mutations improved PFS (HR 0.55; 19.8 vs 16.5 months), with overall-survival data not yet mature.
• Across trials, combination regimens were described as manageable yet produced higher rates of grade ≥3 adverse events and more treatment discontinuations than monotherapy.