Neoadjuvant Osimertinib for Resectable -Mutated Non-Small Cell Lung Cancer.
Journal
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
ISSN
1527-7755
Date Issued
2025-06-02
Author(s)
He, Jianxing
Tsuboi, Masahiro
Weder, Walter
Chen, Ke-Neng
Hochmair, Maximilian J
Lee, Sung Yong
Lee, Kang-Yun
Nhung, Nguyen Viet
Saeteng, Somcharoen
Liu, Lunxu
Xing, Ligang
Gia, Nguyen Hoang
Murakami, Shuji
Han, Yongtao
Saavedra, María Paz
Yoon, Seong Hoon
Teixeira, Carlos H A
Escriu, Carles
Martinez-Marti, Alex
Blakely, Collin M
Yatabe, Yasushi
Dacic, Sanja
Rukazenkov, Yuri
Huang, Xiangning
Dayal, Anupriya
Chaft, Jamie E
Abstract
PURPOSEAdjuvant osimertinib is the standard of care for patients with resected epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). Neoadjuvant treatment could improve surgical and long-term outcomes.METHODSIn this randomized, controlled, phase III study, patients with resectable, EGFR-mutated, stage II-IIIB NSCLC were randomly assigned (1:1:1) to receive neoadjuvant osimertinib (80 mg orally once daily for ≥9 weeks) plus platinum-based chemotherapy (once every 3 weeks for three cycles), osimertinib monotherapy (for ≥9 weeks), or placebo plus platinum-based chemotherapy (control), followed by surgical resection. Adjuvant osimertinib was offered to eligible patients after completion of surgery. The primary end point was major pathologic response (MPR) by blinded central pathology review. Event-free survival (EFS) was a secondary end point.RESULTSOverall, 358 patients were randomly assigned to receive osimertinib plus chemotherapy (121 patients), osimertinib monotherapy (117 patients), or placebo plus chemotherapy (120 patients). Osimertinib plus chemotherapy (MPR rate 26%) and osimertinib monotherapy (25%) demonstrated statistically significant improvement in the MPR rate versus placebo plus chemotherapy (2%), with corresponding odds ratios of 19.82 (95.002% CI, 4.60 to 85.33; P <.0001) and 19.28 (99.9% CI, 1.71 to 217.39; P <.0001), respectively. With 15% data maturity, the EFS rates at 12 months were 93%, 95%, and 83% with osimertinib plus chemotherapy, osimertinib monotherapy, and placebo plus chemotherapy, respectively. In the neoadjuvant period, grade ≥3 adverse events of any cause occurred in 36%, 13%, and 33% of patients with osimertinib plus chemotherapy, osimertinib monotherapy, and placebo plus chemotherapy, respectively. No new safety concerns were identified.CONCLUSIONNeoadjuvant osimertinib with or without chemotherapy demonstrated statistically significant improvement in the MPR rate over chemotherapy alone in patients with resectable, EGFR-mutated, stage II-IIIB NSCLC.
SDGs
Type
journal article