FLAURA2 added chemotherapy to the standard EGFR tablet in 557 patients and cut the risk of the cancer growing by 38 percent, at the cost of chemotherapy's side effects for everybody.
The FLAURA2 investigators, reported by Planchard, Jänne, Cheng and colleagues, randomised 557 patients with previously untreated EGFR-mutated (exon 19 deletion or L858R) advanced non-small-cell lung cancer 1 to 1 between osimertinib 80 mg daily with pemetrexed and platinum chemotherapy, and osimertinib alone. The primary endpoint was investigator-assessed progression-free survival.
It is one of two 2023 and 2024 trials that beat osimertinib monotherapy, the other being MARIPOSA with amivantamab and lazertinib. Both ask the same unresolved question: whether intensifying first-line treatment for everybody is better than keeping a second option in reserve, and for which patients.
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.
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.
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 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 and the tag lung-evidence.
Shares FLAURA: osimertinib as first treatment for EGFR-mutated lung cancer, Oncogene addiction, 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 Pasi A. Jänne, 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 and the tag lung-evidence.
Shares Pasi A. Jänne, Oncogene addiction, 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 Oncogene addiction, 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 MARIPOSA: amivantamab plus lazertinib versus osimertinib as first treatment for EGFR-mutated lung cancer, 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, EGFR-mutated non-small-cell lung cancer and the tag lung-evidence.
Shares MARIPOSA: amivantamab plus lazertinib versus 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, New England Journal of Medicine 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, New England Journal of Medicine, Cisplatin, Carboplatin and the tag lung-evidence.