Osimertinib作为EGFR突变可切除II-IIIB期肺腺癌(NEOS)患者新辅助治疗:一项多中心、单臂、公开的2b期试验

SCI 5 March 2023

Osimertinib as neoadjuvant therapy in patients with EGFR-mutant resectable stage II-IIIB lung adenocarcinoma (NEOS): A multicenter, single-arm, open-label phase 2b trial

（Lung Cancer；IF: 6.081）

Chao Lv, Wentao Fang, Nan Wu, Wenjie Jiao, Shidong Xu, Haitao Ma, Jia Wang, Rui Wang, Chunyu Ji, Shaolei Li, Yuzhao Wang, Shi Yan, Fangliang 

CORRESPONDENCE TO: zlyangyue@bjmu.edu.cn 

Objective 目的  

Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has been approved for EGFR-mutant non-small-cell lung cancer (NSCLC). We aimed to evaluate the efficacy and safety of neoadjuvant osimertinib in patients with EGFR-mutant resectable locally advanced NSCLC. 

Osimertinib是第三代表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI），已被批准用于EGFR突变型非小细胞肺癌（NSCLC）。我们旨在评估新辅助Osimertinib对EGFR突变可切除局部晚期NSCLC患者的疗效和安全性。

Materials and Methods 材料与方法

This single-arm, phase 2b trial (ChiCTR1800016948) was conducted at six centers in mainland China. Patients with a measurable stage IIA-IIIB (T3-4 N2) lung adenocarcinoma and EGFR exon 19 and/or 21 mutations were enrolled. The patients were treated with osimertinib 80 mg orally once per day for six weeks, followed by surgical resection. The primary endpoint was the objective response rate (ORR) assessed according to the Response Evaluation Criteria In Solid Tumors version 1.1.

这项单臂2b期试验（ChiCTR1800016948）在中国大陆的六个中心进行。纳入了具有可测量的IIA-IIIB期（T3-4 N2）肺腺癌和EGFR外显子19和/或21突变的患者。患者每天口服Osimertinib 80mg，为期6周，随后进行手术切除。主要终点是根据1.1版实体瘤临床疗效评价标准评估的客观反应率（ORR）。

Results 结果  

Between October 17, 2018, and June 08, 2021, 88 patients were screened for eligibility. Forty patients were enrolled and treated with neoadjuvant osimertinib therapy. The ORR was 71.1% (27/38) (95% confidence interval: 55.2-83.0) in 38 patients who completed the 6-week osimertinib treatment. Thirty-two patients underwent surgery, and 30 (93.8%) underwent successful R0 resection. Thirty (75.0%) of 40 patients had treatment-related adverse events during neoadjuvant treatment, and three (7.5%) had treatment-related adverse events of grade 3. The most common treatment-related adverse events were rash (n=20 [50%]), diarrhea (n=12 [30%]), and oral ulceration (n=12 [30%]).

2018年10月17日至2021 6月8日，共有88名患者接受了资格筛选。40名患者入选并接受新辅助Osimertinib治疗。在38名完成6周Osimertinib治疗的患者中，ORR为71.1%（27/38）（95%CI：55.2-83.0）。32名患者接受了手术，30名（93.8%）成功接受了R0切除术。40名患者中有30名（75.0%）在新辅助治疗期间发生了治疗相关的不良事件，3名（7.5%）发生了3级治疗相关不良事件。最常见的治疗相关不良事件是皮疹（n=20[50%]）、腹泻（n=12[30%]）和口腔溃疡（n=12[50%]。

Conclusion 结论  

The third-generation EGFR TKI osimertinib, with satisfying efficacy and acceptable safety profile, could be a promising neoadjuvant therapy in patients with resectable EGFR-mutant NSCLC. 

第三代EGFR TKI Osimertinib具有令人满意的疗效和可接受的安全性，可能是可切除EGFR突变NSCLC患者的一种有前途的新辅助疗法。