贝福替在TKI治疗后进展的EGFR T790M突变

Introduction 引言

Befotertinib (D-0316) is a novel, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). This study evaluated befotertinib in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who developed an EGFR T790M mutation after progression on first- or second-generation EGFR TKI therapy.

贝福替尼（befotertinib，D-0316）是一种新型的第三代表皮生长因子受体 (EGFR) 酪氨酸激酶抑制剂 (TKI)。本研究评估了贝福替尼在接受第一代或第二代 EGFR TKI 治疗后出现 EGFR T790M 突变的局部晚期或转移性非小细胞肺癌 (NSCLC) 患者中的疗效。

Methods 方法

这是一项在中国大陆 49 家医院开展的单臂、开放标签、2 期临床研究。在接受第一代或第二代 EGFR TKI 治疗后出现疾病进展的局部晚期或转移性NSCLC患者，每天一次口服 50 mg（队列 A）或 75-100 mg（队列 B）的贝福替尼。主要终点是独立评审委员会 （IRC）在意向治疗人群中评估的客观缓解率 (ORR)。该试验已在 ClinicalTrials.gov 注册，编号为 NCT03861156。

Results 结果

A total of 176 patients and 290 patients were included in cohorts A (50 mg) and B (75-100 mg), respectively. At data-cutoff (August 15, 2021), IRC-assessed ORR was 67.6% (95% confidence interval [CI]: 61.9%-72.9%) in cohort B. The investigator-assessed ORR was 54.0% (95% CI: 46.3%-61.5%) in cohort A and 65.9% (95% CI: 60.1%-71.3%) in cohort B. Investigator-assessed disease control rate was 93.2% (95% CI: 88.4%-96.4%) in cohort A and 94.8% (95% CI: 91.6%-97.1%) in cohort B. Investigator-assessed intracranial ORR was 26.7% (95% CI: 7.8%-55.1%) in cohort A and 57.1% (95% CI: 34.0%-78.2%) in cohort B. The median investigator-assessed progression-free survival (PFS) was 11.0 (95% CI: 9.6-12.5) months in cohort A and 12.5 (95% CI: 11.1-13.8) months in cohort B. The median investigator-assessed intracranial PFS was 16.5 (95% CI: 8.6-not evaluable [NE]) months in cohort A and NE (95% CI: 13.8-NE) in cohort B. The overall survival was immature. Grade 3 or higher treatment-related adverse events and treatment-related serious adverse events occurred in 20.5% and 11.4% of patients in cohort A, and in 29.3% and 10.0% of patients in cohort B, respectively.

共有 176 名患者和 290 名患者分别被纳入队列 A（50 mg）和 B（75-100 mg）。在数据截止时（2021 年 8 月 15 日），队列 B 中 IRC 评估的 ORR 为 67.6%（95% 置信区间 [CI]：61.9%-72.9%）。研究者评估的 ORR 为 54.0%（95% CI：队列 A 为 46.3%-61.5%），队列 B 为 65.9%（95% CI：60.1%-71.3%）。队列 A 中研究者评估的疾病控制率为 93.2%（95% CI：88.4%-96.4%）队列 B 中为 94.8% (95% CI: 91.6%-97.1%)。队列 A 中研究者评估的颅内 ORR 为 26.7% (95% CI: 7.8%-55.1%) 和 57.1% (95% CI: 34.0%) -78.2%) 队列 B。研究者评估的中位无进展生存期 (PFS) 在队列 A 中为 11.0 (95% CI: 9.6-12.5) 个月，在队列 B 中为 12.5 (95% CI: 11.1-13.8) 个月. 队列 A 和队列 B 的中位研究者评估的颅内 PFS 为 16.5 (95% CI: 8.6-不可评估 [NE]) 个月。总生存期不成熟。队列 A 中 20.5% 和 11.4% 的患者发生 3 级或更高级别治疗相关不良事件和治疗相关严重不良事件，队列 B 中分别为 29.3% 和 10.0%。

Conclusion 结论

efotertinib of 75-100 mg has satisfying efficacy and manageable toxicity in patients with locally advanced or metastatic NSCLC harboring T790M mutation with resistance to first- or second- generation EGFR TKIs. A phase 3 randomized trial is underway (NCT04206072).

75-100mg的贝福替尼对第一代或第二代EGFR TKI耐药的局部晚期或转移性 NSCLC 患者具有令人满意的疗效和可控的毒性。3期随机试验正在进行中（NCT04206072）。