He Jianxing, Tsuboi Masahiro, Weder Walter, Chen Ke-Neng, Hochmair Maximilian J, Shih Jin-Yuan, 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
Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China State Key Laboratory of Respiratory Disease & National Clinical Research Centre for Respiratory Disease, Guangzhou, China.
Department of Thoracic Surgery and Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
J Clin Oncol. 2025 Jun 2:JCO2500883. doi: 10.1200/JCO-25-00883.
Adjuvant osimertinib is the standard of care for patients with resected epidermal growth factor receptor ()-mutated non-small cell lung cancer (NSCLC). Neoadjuvant treatment could improve surgical and long-term outcomes.
In this randomized, controlled, phase III study, patients with resectable, -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.
Overall, 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; < .0001) and 19.28 (99.9% CI, 1.71 to 217.39; < .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.
Neoadjuvant osimertinib with or without chemotherapy demonstrated statistically significant improvement in the MPR rate over chemotherapy alone in patients with resectable, -mutated, stage II-IIIB NSCLC.
辅助使用奥希替尼是切除的表皮生长因子受体（EGFR）突变型非小细胞肺癌（NSCLC）患者的标准治疗方案。新辅助治疗可能改善手术及长期预后。
在这项随机、对照、III期研究中，可切除的EGFR突变II-IIIB期NSCLC患者被随机分配（1:1:1）接受新辅助奥希替尼（每日口服80 mg，持续≥9周）加铂类化疗（每3周一次，共三个周期）、奥希替尼单药治疗（持续≥9周）或安慰剂加铂类化疗（对照组），随后进行手术切除。符合条件的患者术后接受辅助奥希替尼治疗。主要终点是经盲法中央病理评估的主要病理缓解（MPR）。无事件生存期（EFS）是次要终点。
总体而言，358例患者被随机分配接受奥希替尼加化疗（121例患者）、奥希替尼单药治疗（117例患者）或安慰剂加化疗（120例患者）。奥希替尼加化疗组（MPR率26%）和奥希替尼单药治疗组（25%）的MPR率与安慰剂加化疗组（2%）相比有统计学显著改善，相应的优势比分别为19.82（95.002%CI，4.60至85.33；P<0.0001）和19.28（99.9%CI，1.71至217.39；P<0.0001）。在数据成熟度为15%时，奥希替尼加化疗组、奥希替尼单药治疗组和安慰剂加化疗组12个月时的EFS率分别为93%、95%和83%。在新辅助治疗期间，奥希替尼加化疗组、奥希替尼单药治疗组和安慰剂加化疗组分别有36%、13%和33%的患者发生任何原因的≥3级不良事件。未发现新的安全问题。
对于可切除的EGFR突变II-IIIB期NSCLC患者，新辅助奥希替尼联合或不联合化疗与单纯化疗相比，MPR率有统计学显著改善。
