一线吡咯替尼治疗晚期 HER2 突变非小细胞肺癌：以患者为中心的 2 期试验

SCI

11 August 2023

First-line pyrotinib in advanced HER2-mutant non-small-cell lung cancer: a patient-centric phase 2 trial

(IF: Nat Med., 82.9)

Liu SM, Tu HY, Wei XW, Yan HH, Dong XR, Cui JW, Zhou Z, Xu CR, Zheng MY, Li YS, Wang Z, Bai XY, Li AN, Sun YL, Huang J, Lin JX, Ke EE, Xu BF, Lu C, Du Y, Chen Y, Ma R, Wang BH, Cang SD, Wang BC, Chen HJ, Yang JJ, Li Y, Zhou Q, Wu YL. First-line pyrotinib in advanced HER2-mutant non-small-cell lung cancer: a patient-centric phase 2 trial. Nat Med. 2023 Jul 24. doi: 10.1038/s41591-023-02461-x. Epub ahead of print. PMID: 37488286.

Correspondence:yangqiuli@hotmail.com; gzzhouqing@126.com; syylwu@live.cn

To explore targeted treatment options in patients with non-small-cell lung cancer (NSCLC) with rare genetic mutations in the context of a patient-centric clinical trial, we initiated, in parallel, a phase 2 adaptive umbrella trial consisting of a criteria-fulfilled (CF) cohort and a compassionate use (CU) cohort under expanded eligibility criteria, and a prospective real-world study (RWS). Here, we present efficacy and safety data from 48 patients with treatment-naive, advanced HER2-mutant NSCLC treated with the pan-HER receptor tyrosine kinase inhibitor pyrotinib (CF and CU cohorts) or physician’s therapy of choice (RWS cohort). In the phase 2 trial CF cohort (n = 28), the primary endpoint was reached with an objective response rate of 35.7% after pyrotinib treatment. Secondary endpoints included disease control rate (89.3%), median progression-free survival (PFS) (7.3 months), median overall survival (OS) (14.3 months) and toxicity, which was acceptable, with grade 3 or 4 treatment-related adverse events occurring in three patients (10.7%). The phase 2 trial CU cohort (n = 12) showed an objective response rate of 16.7%, disease control rate of 83.4%, median PFS of 4.7 months and median OS of 14.2 months after pyrotinib treatment. The RWS cohort (n = 8) had no responses to physician’s therapy of choice, while median PFS and OS were 3.0 and 12.2 months, respectively. 

为了在以患者为中心的临床试验中探索具有非小细胞肺癌（NSCLC）罕见基因突变患者的靶向治疗方案，我们同时启动了一项适应性伞状II期试验，该试验由一个符合标准的（CF）队列和一个符合扩展资格标准的同情使用（CU）队列组成，并进行了一项前瞻性真实世界研究（RWS）。在这里，我们呈现了48名初治的晚期HER2突变NSCLC患者的疗效和安全数据，这些患者接受了泛HER受体酪氨酸激酶抑制剂吡洛替尼（CF和CU队列）或医生选择的治疗方案（RWS队列）。在II期试验CF队列（n=28）中，通过吡洛替尼治疗后达到了主要终点，客观缓解率为35.7%。次要终点包括疾病控制率（89.3%），中位无进展生存期（PFS）（7.3个月），中位总生存期（OS）（14.3个月）和可接受的毒性，其中三名患者（10.7%）出现了3级或4级与治疗相关的不良事件。II期试验CU队列（n=12）显示吡洛替尼治疗后客观缓解率为16.7%，疾病控制率为83.4%，中位PFS为4.7个月，中位OS为14.2个月。RWS队列（n=8）对医生选择的治疗方案未出现响应，而中位PFS和OS分别为3.0和12.2个月。