Lung cancer (Amsterdam, Netherlands) · 2026
Long-term safety of first-line osimertinib plus platinum-pemetrexed in EGFR-mutated advanced NSCLC: FLAURA2.
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Planchard David, Jänne Pasi A, Yang James C-H, Kobayashi Kunihiko, Valdiviezo Natalia, Fan Yun, Kim Tae Min, Gálvez Manuel Leiva, Nishino Kazumi, Biswas Bivas, Feng Po Hao, Sriuranpong Virote, Koubkova Leona, Pinto Gustavo Dix J, Escriu Carles, Tran Tho Vinh, Takahashi Toshiaki, Nerón Yeni, Han Ji-Youn, Figueroa Alejandro, Donachie Vicky, Khullar Anita, Evans Azura, Albayaty Muna, Lee Chee Khoon
Аннотация
INTRODUCTION: In the phase 3 FLAURA2 trial (NCT04035486), adding platinum-pemetrexed to first-line osimertinib significantly improved survival versus osimertinib monotherapy. We report a long-term longitudinal safety analysis, including incidence and temporal patterns of treatment-emergent adverse events (AEs).
METHODS: Patients with EGFR-mutated advanced NSCLC were randomized to either osimertinib plus platinum-pemetrexed (for four cycles, followed by osimertinib plus pemetrexed maintenance), or osimertinib monotherapy. A post-hoc analysis of the combination arm, tailored to individual patients' exposure to each study treatment, was conducted to characterize the safety of three distinct treatment periods: induction (triple-combination therapy; n = 276), pemetrexed-maintenance (osimertinib-plus-pemetrexed; n = 201), and osimertinib-only (n = 206).
RESULTS: In the combination arm, median (range) duration of each period was 2.8 (0.1-4.1), 12.4 (0.7-56.1), and 17.8 (0.4-56.8) months, respectively. Onset frequency of any-grade/grade ≥ 3 AEs causally related to treatment was highest during induction (93%/43%), decreasing progressively across the pemetrexed-maintenance (90%/25%) and osimertinib-only (58%/14%) periods. New AEs indicative of hematological, gastrointestinal, and skin/nail toxicity (mostly grade 1/2) were reported most frequently during induction, with reductions in frequency thereafter. Onset frequency of AEs indicative of renal toxicity was higher during pemetrexed maintenance (19%; all grade 1/2) than induction (7%; one grade 3). Rates of AEs leading to osimertinib discontinuation were low across periods (≤8%).
CONCLUSIONS: By characterizing safety according to individual treatment exposure, this novel analysis provides insight into the longitudinal safety of the FLAURA2 regimen. With prolonged treatment, grade ≥ 3 AE onset frequency progressively declined over successive treatment periods, while AE profiles remained consistent with the known safety profiles of the individual agents. Median durations of the pemetrexed-maintenance and osimertinib-only periods exceeded 12 and 17 months, respectively. This reinforces the favorable long-term benefit-risk profile of the FLAURA2 regimen.
CLINICALTRIALS: gov: NCT04035486.
METHODS: Patients with EGFR-mutated advanced NSCLC were randomized to either osimertinib plus platinum-pemetrexed (for four cycles, followed by osimertinib plus pemetrexed maintenance), or osimertinib monotherapy. A post-hoc analysis of the combination arm, tailored to individual patients' exposure to each study treatment, was conducted to characterize the safety of three distinct treatment periods: induction (triple-combination therapy; n = 276), pemetrexed-maintenance (osimertinib-plus-pemetrexed; n = 201), and osimertinib-only (n = 206).
RESULTS: In the combination arm, median (range) duration of each period was 2.8 (0.1-4.1), 12.4 (0.7-56.1), and 17.8 (0.4-56.8) months, respectively. Onset frequency of any-grade/grade ≥ 3 AEs causally related to treatment was highest during induction (93%/43%), decreasing progressively across the pemetrexed-maintenance (90%/25%) and osimertinib-only (58%/14%) periods. New AEs indicative of hematological, gastrointestinal, and skin/nail toxicity (mostly grade 1/2) were reported most frequently during induction, with reductions in frequency thereafter. Onset frequency of AEs indicative of renal toxicity was higher during pemetrexed maintenance (19%; all grade 1/2) than induction (7%; one grade 3). Rates of AEs leading to osimertinib discontinuation were low across periods (≤8%).
CONCLUSIONS: By characterizing safety according to individual treatment exposure, this novel analysis provides insight into the longitudinal safety of the FLAURA2 regimen. With prolonged treatment, grade ≥ 3 AE onset frequency progressively declined over successive treatment periods, while AE profiles remained consistent with the known safety profiles of the individual agents. Median durations of the pemetrexed-maintenance and osimertinib-only periods exceeded 12 and 17 months, respectively. This reinforces the favorable long-term benefit-risk profile of the FLAURA2 regimen.
CLINICALTRIALS: gov: NCT04035486.