Ryan Jacobs, MD MS

Top lung cancer developments in 2025? My take: 2025 wasn’t about a single disruptive moment. It was about consolidation, maturation, and a few long-awaited signals finally turning solid. 1) MARIPOSA delivers OS Amivantamab + lazertinib demonstrates an overall survival benefit over osimertinib in first-line EGFR-mutant NSCLC. Toxicity, logistics, and sequencing still matter—but this is now a real OS-based conversation, not just a PFS debate. 2) FLAURA2 confirms upfront intensification can matter Osimertinib + chemotherapy shows improved OS vs osimertinib alone. Reinforces that combination strategies can deepen benefit, at the cost of complexity and tolerability. “Best first-line EGFR strategy” is now legitimately plural. 3) HER2 finally matters clinically Accelerated approvals for zongertinib and sevabertinib in HER2-mutant NSCLC. Oral TKIs, meaningful response rates, and a credible path beyond antibody-drug conjugates alone. 4) EGFR exon 20 keeps inching forward Sunvozertinib approved post-platinum. Incremental progress, but still meaningful in a historically difficult molecular subset. 5) c-MET ADC enters routine practice Telisotuzumab vedotin approved for MET-high NSCLC. Expression-based biomarkers and ADCs are now firmly embedded in lung cancer decision-making. 6) A genuine advance in SCLC Tarlatamab converts to full approval in platinum-refractory ES-SCLC with a survival benefit. Rare, and important. 7) Companion diagnostics become unavoidable HER2 TKD, EGFR exon 20, MET expression—therapy is increasingly inseparable from the assay used to define eligibility. Testing strategy is now a core clinical decision. 8) Combination immunotherapy reality check ATR inhibition + durvalumab misses OS (LATIFY). A reminder that biological plausibility still has to survive Phase 3. 9) AI moves from novelty to infrastructure Improved CT nodule detection, risk stratification, and workflow support. Still assistive, not autonomous—but no longer theoretical. 10) Direction of travel is clear More rare targets, more ADCs, OS gains in EGFR-mutant disease, slow but meaningful progress in SCLC—and increasing pressure on systems to deliver precision care at scale. Bottom line: 2025 didn’t reinvent lung cancer. It made several long-promised ideas finally defensible at the OS level. That’s quieter progress—but it’s the kind that lasts. #LCSM @SylvesterCancer @IASLC @myESMO @lungoncdoc @Latinamd @COlazagasti @Jani_Chinmay @NarjustFlorezMD @DrJNaidoo @StephenVLiu @EddieSantosMD @RManochakian @LuisRaezMD @uicc