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Two drugs might work better given in turns rather than together, with less toxicity. Almost no trial has tested this.
Evolutionary models and mouse studies suggest that alternating two non-cross-resistant agents can delay resistance as well as concurrent dosing at lower cumulative toxicity, and that some pairs are antagonistic when concurrent (for example cytostatic agents that protect cells from cytotoxics). Randomised trials of schedule rather than of drug are rare.
For a patient weighing the FLAURA2 regimen against osimertinib alone, the extra toxicity is front-loaded: the hardest months are the four induction cycles, and once pemetrexed stops the profile returns to that of osimertinib by itself. Kidney function deserves watching during pemetrexed maintenance.
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.
One bottleneck page and 18 idea pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
Shares FLAURA2, MARIPOSA: amivantamab plus lazertinib versus osimertinib as first treatment for EGFR-mutated lung cancer, FLAURA: osimertinib as first treatment for EGFR-mutated lung cancer, Too many combinations to test.
Shares FLAURA2, FLAURA: osimertinib as first treatment for EGFR-mutated lung cancer, Too many combinations to test, Osimertinib.
Shares FLAURA: osimertinib as first treatment for EGFR-mutated lung cancer, Osimertinib, Acquired resistance to every therapy, Non-small-cell lung cancer.
Shares FLAURA: osimertinib as first treatment for EGFR-mutated lung cancer, Osimertinib, Non-small-cell lung cancer.
Shares FLAURA2, FLAURA: osimertinib as first treatment for EGFR-mutated lung cancer, Osimertinib, Acquired resistance to every therapy.
Shares Combination Cancer Therapy Can Confer Benefit via Patient-to-Patient Variability without Drug Additivity or Synergy, Too many combinations to test, Acquired resistance to every therapy.
Shares Combination Cancer Therapy Can Confer Benefit via Patient-to-Patient Variability without Drug Additivity or Synergy, Too many combinations to test.
Shares FLAURA2: long-term safety of first-line osimertinib plus platinum-pemetrexed in EGFR-mutated advanced lung cancer, FLAURA2, Osimertinib, Non-small-cell lung cancer.