Overall Survival with Osimertinib in Untreated, EGFR -Mutated Advanced NSCLC

作者：Suresh S. Ramalingam, Johan Vansteenkiste, David Planchard, Byoung Chul Cho, Jhanelle E. Gray, Yuichiro Ohe, Caicun Zhou, Thanyanan Reungwetwattana, Ying Cheng, Busyamas Chewaskulyong, Riyaz Shah, Manuel Cobo, Ki Hyeong Lee, Parneet Cheema, Marcello Tiseo, Thomas John, Meng‐Chih Lin, Fumio Imamura, Takayasu Kurata, Alexander Todd, Rachel Hodge, Matilde Saggese, Yuri Rukazenkov, Jean‐Charles Soria · 发表于：New England Journal of Medicine · 年份：2019 · DOI：10.1056/nejmoa1913662 · 被引用次数：2925 · 研究领域：Lung Cancer Treatments and Mutations、Fibroblast Growth Factor Research、Lung Cancer Diagnosis and Treatment

BACKGROUNDOsimertinib is a third-generation, irreversible tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR-TKI) that selectively inhibits both EGFR-TKIsensitizing and EGFR T790M resistance mutations.A phase 3 trial compared firstline osimertinib with other EGFR-TKIs in patients with EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC).The trial showed longer progressionfree survival with osimertinib than with the comparator EGFR-TKIs (hazard ratio for disease progression or death, 0.46).Data from the final analysis of overall survival have not been reported. METHODSIn this trial, we randomly assigned 556 patients with previously untreated advanced NSCLC with an EGFR mutation (exon 19 deletion or L858R allele) in a 1:1 ratio to receive either osimertinib (80 mg once daily) or one of two other EGFR-TKIs (gefitinib at a dose of 250 mg once daily or erlotinib at a dose of 150 mg once daily, with patients receiving these drugs combined in a single comparator group).Overall survival was a secondary end point. RESULTSThe median overall survival was 38.6 months (95% confidence interval [CI], 34.5 to 41.8) in the osimertinib group and 31.8 months (95% CI, 26.6 to 36.0) in the comparator group (hazard ratio for death, 0.80; 95.05% CI, 0.64 to 1.00; P = 0.046).At 3 years, 79 of 279 patients (28%) in the osimertinib group and 26 of 277 (9%) in the comparator group were continuing to receive a trial regimen; the median exposure was 20.7 months and 11.5...