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Combining an EGFR-MET bispecific antibody with a third-generation EGFR pill beat osimertinib alone, delaying progression by about seven months and later improving survival, at the cost of more side effects.
Phase 3 trial of 1,074 patients with untreated EGFR-mutated (exon 19 deletion or L858R) advanced NSCLC, randomised 2:2:1 to amivantamab plus lazertinib, osimertinib, or lazertinib alone. Primary endpoint was PFS by blinded review for the combination versus osimertinib.
Median PFS was 23.7 vs 16.6 months (HR 0.70). A 2025 final overall survival analysis reported a significant improvement (HR about 0.75) with median survival in the combination arm not reached and projected to exceed osimertinib by more than a year. It is the first regimen to beat osimertinib on survival, but adds infusion reactions, venous thromboembolism, rash and paronychia.
Patients newly diagnosed with EGFR-mutated advanced lung cancer now have a first-line option that improves survival over osimertinib, particularly if they have high-risk features. The trade-off is intravenous (now subcutaneous) infusions and considerably more skin, nail and clotting toxicity, so osimertinib alone remains reasonable for those who prioritise convenience and tolerability. Both this regimen and osimertinib plus chemotherapy (FLAURA2) are approved; there is no direct comparison.
Adding chemotherapy to osimertinib delays progression. Whether it extends life, and whether the same benefit could be had by giving the chemotherapy later to the patients who need it, is what the overall survival analysis and the registry watch on this roadmap are for.
A rare driver with a real drug, and a warning about biomarker thresholds: the same gene, tested the same way, predicts response or does not depending on a copy-number cut-off that has to be measured rather than assumed.
Anyone diagnosed with advanced lung cancer should have EGFR testing before treatment, because osimertinib as the first drug gives the longest disease control, protects the brain, and is well tolerated. Chemotherapy is not the first step for these patients. The remaining questions are whether to intensify upfront (adding chemotherapy or amivantamab) and how to treat resistance when it develops.
Shares Make resistance a diagnosis: sequence at every progression and choose the next line from what the tumour became, Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors, Driver mutation, Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch.
Shares MARIPOSA, FLAURA2, FLAURA: osimertinib as first treatment for EGFR-mutated lung cancer, Amivantamab.
Shares MARIPOSA, Lazertinib, Amivantamab, MET.
Shares MARIPOSA, Lazertinib, Amivantamab, MET.
Shares Test alternating drug schedules against giving both drugs at once, FLAURA2, Lines of therapy, Osimertinib.
Shares FLAURA: osimertinib as first treatment for EGFR-mutated lung cancer, Driver mutation, Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch, Osimertinib.
Shares Shun Lu, Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch, Osimertinib, Prices and value.
Shares Make resistance a diagnosis: sequence at every progression and choose the next line from what the tumour became, Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors, Driver mutation, MET.