Yu Yongfeng, Guo Qisen, Zhang Yongchang, Fang Jian, Zhong Diansheng, Liu Baogang, Pan Pinhua, Lv Dongqing, Wu Lin, Zhao Yanqiu, Li Juan, Liu Zhihua, Liu Chunling, Su Haichuan, Fan Yun, Zhang Tongmei, Liu Anwen, Jin Bo, Wang Ye, Zhou Jianying, Zhang Zhihong, Ran Fengming, Song Xia, Shi Michael, Su Weiguo, Lu Shun
Department of Medical Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Medical Oncology, Shandong Cancer Hospital, Jinan, China.
Lancet Respir Med. 2024 Dec;12(12):958-966. doi: 10.1016/S2213-2600(24)00211-X. Epub 2024 Sep 10.
Savolitinib has been approved in China for advanced or metastatic non-small-cell lung cancer (NSCLC) with MET exon 14 (METex14) skipping alterations in previously treated patients and those unable to receive platinum-based chemotherapy. We report results from a treatment-naive cohort of a phase 3b study that was designed to evaluate the efficacy and safety of savolitinib in locally advanced or metastatic METex14-mutated NSCLC.
This single-arm, multicohort, multicentre, open-label, phase 3b study was done at 48 hospitals in China in adult (≥18 years) patients with locally advanced or metastatic METex14-mutated NSCLC who had not received previous systemic antitumour therapy. Patients with a bodyweight of 50 kg or more and those with a bodyweight of less than 50 kg received savolitinib once daily at 600 mg or 400 mg, respectively, in 21-day cycles. The primary endpoint was objective response rate assessed by independent review committee (IRC) per Response Evaluation Criteria in Solid Tumours, version 1.1. The full analysis set comprised all patients who received at least one dose of study medication, which was used to assess the efficacy endpoints and baseline and safety data. This study is registered with ClinicalTrials.gov (NCT04923945) and is closed to accrual.
Between Aug 31, 2021, and Oct 20, 2023, 125 treatment-naive patients were assessed for eligibility, of whom 87 were enrolled and received savolitinib. The median age of patients was 70·0 years (IQR 65·2-75·8) and 51 (59%) of 87 patients were male and 36 (41%) were female. In the full analysis set, the IRC-assessed objective response rate was 62% (95% CI 51-72) and the investigator-assessed objective response rate was 60% (49-70), showing a high concordance rate (84%). Treatment-related adverse events were reported in 85 (98%) of 87 patients, with peripheral oedema (54 [62%]) being the most common. Two of these treatment-related adverse events led to death (cardiac failure n=1, unknown reasons n=1).
Savolitinib showed manageable toxicity and promising efficacy in treatment-naive patients with advanced or metastatic METex14-mutated NSCLC.
HUTCHMED and AstraZeneca.
赛沃替尼已在中国获批用于治疗既往接受过治疗且无法接受铂类化疗的、具有MET外显子14（METex14）跳跃改变的晚期或转移性非小细胞肺癌（NSCLC）患者。我们报告了一项3b期研究中初治队列的结果，该研究旨在评估赛沃替尼治疗局部晚期或转移性METex14突变NSCLC的疗效和安全性。
这项单臂、多队列、多中心、开放标签的3b期研究在中国48家医院开展，纳入年龄≥18岁、局部晚期或转移性METex14突变且未接受过全身抗肿瘤治疗的NSCLC成年患者。体重≥50 kg的患者和体重<50 kg的患者分别接受赛沃替尼每日一次，剂量为600 mg或400 mg，每21天为一个周期。主要终点是根据实体瘤疗效评价标准1.1版由独立审查委员会（IRC）评估的客观缓解率。完整分析集包括所有接受至少一剂研究药物的患者，用于评估疗效终点以及基线和安全性数据。本研究已在ClinicalTrials.gov注册（NCT04923945），现已停止入组。
在2021年8月31日至2023年10月20日期间，对125例初治患者进行了资格评估，其中87例入组并接受了赛沃替尼治疗。患者的中位年龄为70.0岁（四分位间距65.2 - 75.8），87例患者中51例（59%）为男性，36例（41%）为女性。在完整分析集中，IRC评估的客观缓解率为62%（95%CI 51 - 72），研究者评估的客观缓解率为60%（49 - 70），一致性较高（84%）。87例患者中有85例（98%）报告了与治疗相关的不良事件，其中外周水肿最为常见（54例[62%]）。这些与治疗相关的不良事件中有2例导致死亡（心力衰竭1例，原因不明1例）。
赛沃替尼在初治的晚期或转移性METex14突变NSCLC患者中显示出可控的毒性和有前景的疗效。
和黄医药与阿斯利康。
