Overview

• Final FLAURA2 results showed first-line osimertinib plus platinum–pemetrexed extended median overall survival to 47.5 months versus 37.6 with monotherapy (HR 0.77; p=0.02).
• COMPEL demonstrated that continuing osimertinib with platinum–pemetrexed after non‑CNS progression prolonged median progression-free survival to 8.4 months versus 4.4 (HR 0.43) and delivered a numerically longer overall survival (15.9 vs 9.8 months; HR 0.71, CI crossing 1).
• HARMONi found ivonescimab plus chemotherapy improved median progression-free survival after third‑generation EGFR TKI failure to 6.8 months versus 4.4 (HR 0.52; P<0.001) with a positive overall survival trend (16.8 vs 14.0 months; HR 0.79; P=0.057).
• Across trials, grade ≥3 adverse events were more frequent with combination regimens, yet safety profiles were reported as manageable and consistent with known effects.
• ACROSS 2 reported longer progression-free survival with aumolertinib plus chemotherapy in patients with tumor suppressor gene co‑mutations (19.8 vs 16.5 months; HR 0.55) alongside higher treatment-emergent toxicities.