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The first randomised test of a KRAS inhibitor. Sotorasib beat docetaxel on time to progression by about a month, with fewer serious side effects. A real but modest win against the commonest driver in lung cancer.
The CodeBreaK 200 investigators, reported by de Langen, Johnson, Mazieres and colleagues, randomised 345 patients with KRAS G12C-mutated advanced non-small-cell lung cancer who had progressed after platinum chemotherapy and a PD-1 or PD-L1 inhibitor to oral sotorasib 960 mg daily (171) or intravenous docetaxel 75 mg per square metre every three weeks (174), across 148 centres in 22 countries.
KRAS was undruggable for thirty years, and the G12C covalent inhibitors are the proof that it is not. Set against that, CodeBreaK 200's 1.1-month gain in median progression-free survival, with no overall survival benefit, is a sober reminder that hitting a target is not the same as controlling a disease.
KRAS is druggable, and the first generation of drugs is not very good. The gap between the biological achievement and the clinical gain is what the next generation of KRAS inhibitors, and the combination trials around them, exist to close.
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 Solange Peters, 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 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, Acquired resistance to every therapy and the tag lung-evidence.
Shares Luis Paz-Ares, Amgen, 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 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, The undruggable drivers, RAS / RAF / MEK / ERK (MAPK) 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, Drug resistance (primary and acquired), Acquired resistance to every therapy 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, KRAS, Lung cancer (all types) 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, Lung cancer (all types) and the tag lung-evidence.