治疗未接受过治疗的ALK阳性非小细胞肺癌的Envonalkib与crizotinib：一项随机、多中心、开放标签的III期试验。
Envonalkib versus crizotinib for treatment-naive ALK-positive non-small cell lung cancer: a randomized, multicenter, open-label, phase III trial.
发表日期：2023 Aug 14
作者：
Yunpeng Yang, Jie Min, Nong Yang, Qitao Yu, Ying Cheng, Yanqiu Zhao, Manxiang Li, Hong Chen, Shou'an Ren, Jianying Zhou, Wu Zhuang, Xintian Qin, Lejie Cao, Yan Yu, Jian Zhang, Jianxing He, Jifeng Feng, Hao Yu, Li Zhang, Wenfeng Fang
来源：
Signal Transduction and Targeted Therapy
摘要：
非小细胞肺癌（NSCLC）中大约有5-6％的病例存在无形淋巴瘤激酶（ALK）重排，并与中枢神经系统（CNS）参与的风险增加有关。Envonalkib是一种新型ALK抑制剂，在先人类一期临床研究中展示了有希望的抗肿瘤活性和安全性，适用于晚期ALK阳性NSCLC治疗。该三期临床试验（ClinicalTrials.gov NCT04009317）研究了一线Envonalkib在晚期ALK阳性NSCLC病例中的疗效和安全性。共有264名参与者以1：1的比例随机分配，分别接受Envonalkib（n = 131）或克唑替尼（n = 133）。Envonalkib组和克唑替尼组的中位独立评议委员会（IRC）评估的无进展生存期（PFS）时间分别为24.87个月（95％置信区间[CI]：15.64-30.36）和11.60个月（95％CI：8.28-13.73）（风险比[HR] = 0.47，95％CI：0.34-0.64，p < 0.0001）。IRC评估的确证客观缓解率（ORR）在Envonalkib组中较高（81.68％对70.68％，p = 0.056），且缓解持续时间更长（中位数，25.79 [95％CI，16.53-29.47] vs. 11.14 [95％CI，9.23-16.59] 个月，p = 0.0003）。在具有基线脑病变靶标的参与者中，IRC评估的CNS-ORR与Envonalkib相比改善明显（78.95％对23.81％）。总体生存（OS）数据尚未成熟，Envonalkib和克唑替尼组的中位OS均未达到（HR = 0.84，95％CI：0.48-1.47，p = 0.5741）。12个月OS率分别为90.6％（95％CI，84.0％-94.5％）和89.4％（95％CI，82.8％-93.6％）（Envonalkib组和克唑替尼组）。Envonalkib组和克唑替尼组的≥3级与治疗相关的不良事件分别观察到55.73％和42.86％的参与者。Envonalkib显著改善了ALK阳性NSCLC患者的PFS并推迟了脑转移进展。©2023. 四川大学华西医院.
Anaplastic lymphoma kinase (ALK) rearrangements are present in about 5-6% of non-small cell lung cancer (NSCLC) cases and associated with increased risks of central nervous system (CNS) involvement. Envonalkib, a novel ALK inhibitor, demonstrated promising anti-tumor activity and safety in advanced ALK-positive NSCLC in the first-in-human phase I study. This phase III trial (ClinicalTrials.gov NCT04009317) investigated the efficacy and safety of first-line envonalkib in advanced ALK-positive NSCLC cases. Totally 264 participants were randomized 1:1 to receive envonalkib (n = 131) or crizotinib (n = 133). Median independent review committee (IRC)-assessed progression-free survival (PFS) times were 24.87 (95% confidence interval [CI]: 15.64-30.36) and 11.60 (95% CI: 8.28-13.73) months in the envonalkib and crizotinib groups, respectively (hazard ratio [HR] = 0.47, 95% CI: 0.34-0.64, p < 0.0001). IRC-assessed confirmed objective response rate (ORR) was higher (81.68% vs. 70.68%, p = 0.056) and duration of response was longer (median, 25.79 [95% CI, 16.53-29.47] vs. 11.14 [95% CI, 9.23-16.59] months, p = 0.0003) in the envonalkib group compared with the crizotinib group. In participants with baseline brain target lesions, IRC-assessed CNS-ORR was improved with envonalkib compared with crizotinib (78.95% vs. 23.81%). Overall survival (OS) data were immature, and median OS was not reached in either group (HR = 0.84, 95% CI: 0.48-1.47, p = 0.5741). The 12-month OS rates were 90.6% (95% CI, 84.0%-94.5%) and 89.4% (95% CI, 82.8%-93.6%) in the envonalkib and crizotinib groups, respectively. Grade ≥3 treatment-related adverse events were observed in 55.73% and 42.86% of participants in the envonalkib and crizotinib groups, respectively. Envonalkib significantly improved PFS and delayed brain metastasis progression in advanced ALK-positive NSCLC.© 2023. West China Hospital, Sichuan University.