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Side effects of the osimertinib plus chemotherapy combination were most frequent in the first four chemotherapy cycles and fell steadily once patients moved to maintenance and then to osimertinib alone; few had to stop osimertinib because of them.
Post hoc longitudinal safety analysis of the combination arm of FLAURA2, the phase 3 trial in which adding platinum-pemetrexed to first-line osimertinib improved survival over osimertinib alone in EGFR-mutated advanced non-small-cell lung cancer. Adverse events were analysed by each patient's exposure to three treatment periods: induction with the triple combination (276 patients), pemetrexed maintenance with osimertinib (201) and osimertinib alone after pemetrexed stopped (206).
Median durations of the three periods were 2.8, 12.4 and 17.8 months. Onset of any-grade and grade 3 or worse treatment-related adverse events was highest during induction (93 percent and 43 percent), lower during pemetrexed maintenance (90 percent and 25 percent) and lowest on osimertinib alone (58 percent and 14 percent). New haematological, gastrointestinal and skin or nail events, mostly grade 1 or 2, clustered in induction; renal events were more frequent during pemetrexed maintenance (19 percent, all grade 1 or 2) than induction (7 percent). Adverse events leading to osimertinib discontinuation were 8 percent or fewer in every period.
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.
Shares David Planchard, Pasi A. Jänne, FLAURA2, Osimertinib.
Shares Osimertinib, EGFR-mutated non-small-cell lung cancer, AstraZeneca, Non-small-cell lung cancer.
Shares Osimertinib, EGFR-mutated non-small-cell lung cancer, EGFR, AstraZeneca.
Shares Osimertinib, EGFR-mutated non-small-cell lung cancer, AstraZeneca, Non-small-cell lung cancer.
Shares Osimertinib, EGFR-mutated non-small-cell lung cancer, AstraZeneca, Non-small-cell lung cancer.
Shares Lung cancer, Non-small-cell lung cancer.
Shares Osimertinib, EGFR-mutated non-small-cell lung cancer, AstraZeneca, Non-small-cell lung cancer.
Shares Test alternating drug schedules against giving both drugs at once, FLAURA2, Lines of therapy, Osimertinib.