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Adding chemotherapy to osimertinib extended both progression-free and, in 2025, overall survival.
FLAURA2, trial NCT04035486 sponsored by AstraZeneca and published in the New England Journal of Medicine in 2023, showed that adding platinum chemotherapy to first-line osimertinib in EGFR-mutant non-small-cell lung cancer extends progression-free survival and, in 2025, overall survival. It randomised 557 patients to osimertinib with or without chemotherapy and met its primary investigator-assessed progression-free survival endpoint, with the survival benefit reported later. OnCo links it to non-small-cell lung cancer, osimertinib, Suresh S. Ramalingam, Pasi A. Jänne, Guangdong Provincial People's Hospital, FURLONG, the bottleneck of acquired resistance, the idea of alternating schedules and the FLAURA and MARIPOSA papers. The two regimens have never been compared directly, and which patients need intensification is the open question.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
587 enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Progression-free survival (investigator)primary | Osimertinib + chemotherapy | 279 | 25.5 months | 0.62 (0.49 to 0.79) | <0.001 | link |
| Osimertinib | 278 | 16.7 months | ||||
| Overall survival | Osimertinib + chemotherapy | - | 47.5 months | 0.77 (0.61 to 0.96) | 0.02 | link |
| Osimertinib | - | 37.6 months |
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.
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.
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 Suresh S. Ramalingam, Autonomous closed-loop adaptive therapy driven by blood tests and evolutionary models, Add the second drug on day one when the escape route is predictable, FLAURA: osimertinib as first treatment for EGFR-mutated lung cancer.
Shares Autonomous closed-loop adaptive therapy driven by blood tests and evolutionary models, Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall, Osimertinib, EGFR-mutated non-small-cell lung cancer.
Shares Add the second drug on day one when the escape route is predictable, MARIPOSA: amivantamab plus lazertinib versus osimertinib as first treatment for EGFR-mutated lung cancer, FLAURA: osimertinib as first treatment for EGFR-mutated lung cancer, Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall.
Shares Suresh S. Ramalingam, FLAURA: osimertinib as first treatment for EGFR-mutated lung cancer, Osimertinib, Acquired resistance to every therapy.
Shares Autonomous closed-loop adaptive therapy driven by blood tests and evolutionary models, Osimertinib, EGFR-mutated non-small-cell lung cancer, AstraZeneca.
Shares FLAURA: osimertinib as first treatment for EGFR-mutated lung cancer, Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall, Osimertinib, Acquired resistance to every therapy.
Shares FLAURA2: long-term safety of first-line osimertinib plus platinum-pemetrexed in EGFR-mutated advanced lung cancer, Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC, EGFR-mutated non-small-cell lung cancer, Non-small-cell lung cancer.
Shares Autonomous closed-loop adaptive therapy driven by blood tests and evolutionary models, Guangdong Provincial People's Hospital, Add the second drug on day one when the escape route is predictable, FLAURA: osimertinib as first treatment for EGFR-mutated lung cancer.