Osimertinib with or without Chemotherapy in EGFR -Mutated Advanced NSCLC

作者：David Planchard, Pasi A. Jänne, Ying Cheng, James Chih‐Hsin Yang, Noriko Yanagitani, Sang‐We Kim, Shunichi Sugawara, Yan Yu, Yun Fan, Sarayut Lucien Geater, К. К. Лактионов, Chee Khoon Lee, Natalia Valdiviezo, Samreen Ahmed, Jean-Marc Maurel, Igor Andrašina, Jonathan W. Goldman, Dana Ghiorghiu, Yuri Rukazenkov, Alex Todd, Kunihiko Kobayashi · 发表于：New England Journal of Medicine · 年份：2023 · DOI：10.1056/nejmoa2306434 · 被引用次数：714 · 研究领域：Lung Cancer Treatments and Mutations、Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Lung Cancer Diagnosis and Treatment

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. Research Summary Osimertinib with or without Chemotherapy in EGFR -Mutated Advanced NSCLC 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 al...