1. Osimertinib with or without Chemotherapy in EGFR -Mutated Advanced NSCLC.
- Author
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Planchard D, Jänne PA, Cheng Y, Yang JC, Yanagitani N, Kim SW, Sugawara S, Yu Y, Fan Y, Geater SL, Laktionov K, Lee CK, Valdiviezo N, Ahmed S, Maurel JM, Andrasina I, Goldman J, Ghiorghiu D, Rukazenkov Y, Todd A, and Kobayashi K
- Subjects
- Humans, Aniline Compounds adverse effects, Antineoplastic Combined Chemotherapy Protocols adverse effects, ErbB Receptors genetics, Mutation, Pemetrexed adverse effects, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Protein Kinase Inhibitors adverse effects, Protein Kinase Inhibitors therapeutic use, Antineoplastic Agents therapeutic use
- Abstract
Background: Osimertinib is a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) that is selective for EGFR-TKI-sensitizing and EGFR T790M resistance mutations. Evidence suggests that the addition of chemotherapy may extend the benefits of EGFR-TKI therapy., Methods: In this phase 3, international, open-label trial, we randomly assigned in a 1:1 ratio patients with EGFR -mutated (exon 19 deletion or L858R mutation) advanced non-small-cell lung cancer (NSCLC) who had not previously received treatment for advanced disease to receive osimertinib (80 mg once daily) with chemotherapy (pemetrexed [500 mg per square meter of body-surface area] plus either cisplatin [75 mg per square meter] or carboplatin [pharmacologically guided dose]) or to receive osimertinib monotherapy (80 mg once daily). The primary end point was investigator-assessed progression-free survival. Response and safety were also assessed., Results: A total of 557 patients underwent randomization. Investigator-assessed progression-free survival was significantly longer in the osimertinib-chemotherapy group than in the osimertinib group (hazard ratio for disease progression or death, 0.62; 95% confidence interval [CI], 0.49 to 0.79; P<0.001). At 24 months, 57% (95% CI, 50 to 63) of the patients in the osimertinib-chemotherapy group and 41% (95% CI, 35 to 47) of those in the osimertinib group were alive and progression-free. Progression-free survival as assessed according to blinded independent central review was consistent with the primary analysis (hazard ratio, 0.62; 95% CI, 0.48 to 0.80). An objective (complete or partial) response was observed in 83% of the patients in the osimertinib-chemotherapy group and in 76% of those in the osimertinib group; the median response duration was 24.0 months (95% CI, 20.9 to 27.8) and 15.3 months (95% CI, 12.7 to 19.4), respectively. The incidence of grade 3 or higher adverse events from any cause was higher with the combination than with monotherapy - a finding driven by known chemotherapy-related adverse events. The safety profile of osimertinib plus pemetrexed and a platinum-based agent was consistent with the established profiles of the individual agents., Conclusions: First-line treatment with osimertinib-chemotherapy led to significantly longer progression-free survival than osimertinib monotherapy among patients with EGFR -mutated advanced NSCLC. (Funded by AstraZeneca; FLAURA2 ClinicalTrials.gov number, NCT04035486.)., (Copyright © 2023 Massachusetts Medical Society.)
- Published
- 2023
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