贝福替尼对比埃克替尼作为EGFR突变局部晚期或转移性非小细胞肺癌患者的一线治疗：一项多中心、开放、随机的Ⅲ期临床研究

SCI

25 May 2023

Befotertinib (D-0316) versus icotinib as first-line therapy for patients with EGFR-mutated locally advanced or metastatic non-small-cell lung cancer: a multicentre, open-label, randomised phase 3 study

（LANCET RESP MED；IF：102.642）

S. Lu, J. Zhou, H. Jian, L. Wu, Y. Cheng, Y. Fan, et al.The Lancet Respiratory Medicine DOI: 10.1016/S2213-2600(23)00183-2

Correspondence to: Prof Shun Lu, Department of Medical Oncology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China

shunlu@sjtu.edu.cn or Prof Jianying Zhou, Department of Respiratory Medicine, First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310003, China

zjyhz@zju.edu.cn

Background 背景

Befotertinib (D-0316) is a novel, selective oral third-generation epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor. This phase 3 trial compared the efficacy and safety of befotertinib with icotinib as a first-line treatment for patients with EGFR mutation-positive locally advanced or metastatic non-small-cell lung cancer (NSCLC).

贝福替尼 (D-0316) 是一种新型的选择性口服第三代表皮生长因子受体（EGFR）酪氨酸激酶抑制剂。这项Ⅲ期试验比较了贝福替尼和埃克替尼作为EGFR突变阳性的局部晚期或转移性非小细胞肺癌癌症患者一线治疗的疗效和安全性。

Methods 方法  

This study was a multicentre, open-label, randomised, controlled phase 3 study at 39 hospitals in China. Eligible patients were 18 years of age or older, had histologically confirmed locally advanced or metastatic stage IIIB, IIIC, or IV unresectable NSCLC, and had confirmed exon 19 deletions or exon 21 Leu858Arg mutation. Patients were randomly assigned (1:1) via an interactive web response system to receive either oral befotertinib (75–100 mg once daily) or oral icotinib (125 mg three times per day) in 21-day cycles until disease progression or withdrawal criteria were met. Randomisation was stratified by type of EGFR mutation, CNS metastasis status, and gender, and participants, investigators, and data analysts were not masked to treatment allocation. The primary endpoint was independent review committee (IRC)-assessed progression-free survival in the full analysis set, which comprised all randomly assigned patients. All patients who received at least one dose of the study drug were included in safety analyses. This study was registered with ClinicalTrials.gov, NCT04206072, and the overall survival follow-up is still in progress.

本研究是一项在中国39家医院开展的多中心、开放、随机、对照的III期临床研究。符合条件的患者年龄为18岁或以上，经组织学证实为局部晚期或转移性IIIB、IIIC期或IV期不可切除的NSCLC，并已确认19号外显子缺失或21号外显子Leu858Arg点突变。患者通过交互式网络响应系统1:1随机分配，在21天的周期内接受口服贝福替尼（75–100 mg，每天一次）或口服埃克替尼（125 mg，每天三次），直到疾病进展或达到病例退出标准。根据EGFR突变类型、中枢神经系统转移状态和性别对随机分组进行分层，治疗分配结果不对参与者、研究人员和数据分析人员设盲。主要研究终点是独立评审委员会（IRC）评估的完整分析集中的无进展生存期，该分析包含了所有随机分配的患者。所有至少接受一剂研究药物的患者均纳入安全性分析。本研究已在美国临床试验网站ClinicalTrials.gov上注册，NCT04206072，总生存期的随访仍在进行中。

Findings 研究结果  

Between Dec 24, 2019, and Dec 18, 2020, 568 patients were screened, of whom 362 were randomly assigned to the befotertinib (n=182) or icotinib (n=180) group; all 362 patients were included in the full analysis set. Median follow-up was 20.7 months (IQR 10.2–23.5) in the befotertinib group and 19.4 months (10.3–23.5) in the icotinib group. Median IRC-assessed progression-free survival was 22.1 months (95% CI 17.9–not estimable) in the befotertinib group and 13.8 months (12.4–15.2) in the icotinib group (hazard ratio 0.49 [95% CI 0.36–0.68], p<0.0001). Grade 3 or higher treatment-related adverse events occurred in 55 (30%) of 182 patients in the befotertinib group and in 14 (8%) of 180 patients in the icotinib group. Treatment-related serious adverse events were reported in 37 (20%) patients in the befotertinib group and in five (3%) patients in the icotinib group. Two (1%) patients in the befotertinib group and one (1%) patient in the icotinib group died due to treatment-related adverse events.

在2019年12月24日至2020年12月18日期间，对568名患者进行了筛查，其中362名患者被随机分配到贝福替尼组（182例）或埃克替尼组（180例）；所有362名患者均纳入整个分析集。贝福替尼组的中位随访时间为20.7个月（IQR10.2–23.5），埃克替尼组的中位随访时间为19.4个月（10.3–23.5）。贝福替尼组的IRC评估的中位无进展生存期为22.1个月（95％CI 17.9–无法估计），埃克替尼组的为13.8个月（12.4–15.2）（危险比0.49 [95％ CI 0.36–0.68]，P<0.0001）。贝福替尼组182名患者中有55名（30%）出现3级或更高的治疗相关不良事件，埃克替尼组180名患者中有14名（8%）出现3级或更高的治疗相关不良事件。贝福替尼组报道了37例（20%）患者和埃克替尼组报道了5例（3%）患者出现与治疗相关的严重不良事件。贝福替尼组有2名（1%）患者和埃克替尼组有1名（1%）患者死于治疗相关不良事件。

Interpretation 说明  

Befotertinib demonstrated superior efficacy compared with icotinib in first-line treatment for patients with EGFR mutation-positive NSCLC. Although serious adverse events were more common in the befotertinib than the icotinib arm, the safety profile of befotertinib was manageable overall.

在EGFR突变阳性非小细胞肺癌患者的一线治疗中，贝福替尼与埃克替尼相比显示出优越的疗效。尽管比埃克替尼的严重不良事件更常见，但贝福替尼的安全性总体上是可控的。

打赏