Loading
MARIPOSA beat osimertinib, the standard first treatment, by about seven months before the cancer grew again. It is the first trial to do so, and the first to show that hitting EGFR two ways at once is better than one.
The MARIPOSA investigators, reported by Cho, Lu, Felip and colleagues, randomised 1,074 patients with previously untreated EGFR-mutated (exon 19 deletion or L858R) locally advanced or metastatic non-small-cell lung cancer 2 to 2 to 1 between amivantamab with lazertinib (open-label), osimertinib (blinded) and lazertinib alone (blinded, to assess the contribution of each component). The primary endpoint was blinded independent central review progression-free survival against osimertinib.
The third arm is the methodological point: a combination trial that can say whether the combination is better than either of its parts, rather than only better than the comparator. The cost is toxicity, and the discontinuation figures are the argument against giving it to everybody.
The first regimen to beat osimertinib as first-line treatment for EGFR-mutant lung cancer. It sets up the choice that now faces every newly diagnosed patient: a more effective but harder combination now, or a simpler tablet with something held back for later.
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 and the tag lung-evidence.
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 and the tag lung-evidence.
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, Acquired resistance to every therapy and the tag lung-evidence.
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, EGFR-mutated non-small-cell lung cancer and the tag lung-evidence.
Shares Driver mutation, Too many combinations to test, 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, Drug resistance (primary and acquired) and the tag lung-evidence.
Shares 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, Drug resistance (primary and acquired), Acquired resistance to every therapy, Toxicity and quality of life are undervalued and the tag lung-evidence.
Shares 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, EGFR-mutated non-small-cell lung cancer, EGFR and the tag lung-evidence.
Shares 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, EGFR-mutated non-small-cell lung cancer, EGFR and the tag lung-evidence.