Kudo Masatoshi, Finn Richard S, Ikeda Masafumi, Sung Max W, Baron Ari D, Okusaka Takuji, Kobayashi Masahiro, Kumada Hiromitsu, Kaneko Shuichi, Pracht Marc, Meyer Tim, Nagao Satoshi, Saito Kenichi, Mody Kalgi, Ramji Zahra, Dubrovsky Leonid, Llovet Josep M
Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan.
Department of Gastroenterology and Hepatology, Geffen School of Medicine, UCLA Medical Center, Santa Monica, CA, USA.
Liver Cancer. 2023 Nov 13;13(4):451-458. doi: 10.1159/000535154. eCollection 2024 Aug.
Lenvatinib (dosing for patients who weigh ≥60 kg was 12 mg/day; for patients who weigh <60 kg, the dose was 8 mg/day) plus pembrolizumab 200 mg once every 3 weeks demonstrated antitumor activity and a manageable safety profile in patients with first-line unresectable hepatocellular carcinoma (uHCC) in the open-label phase 1b Study 116/KEYNOTE-524 (primary analysis data cutoff date: October 31, 2019; median follow-up: 10.6 months). This analysis (updated data cutoff date: March 31, 2021) reports efficacy results from 17 months of additional follow-up time.
100 patients with uHCC were included in the primary analysis (median follow-up: 27.6 months). Endpoints included overall survival (OS), investigator-assessed progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR) per modified RECIST. Landmark analyses of OS by the best response at 3 and 9 months were performed. Pembrolizumab antidrug antibodies (ADAs) and concentrations were also measured (cutoff date: August 7, 2020).
ORR was 43.0% (95% CI 33.1-53.3%) and median DOR was 17.1 months (95% CI 6.9-19.3 months). Median PFS and OS were 9.3 months (95% CI 7.4-9.8 months) and 20.4 months (95% CI 14.4-25.9 months), respectively. No treatment-emergent ADAs were detected.
Results show a sustained treatment effect with lenvatinib plus pembrolizumab in patients with uHCC in the first-line setting.
在开放标签的1b期研究116/KEYNOTE - 524中（主要分析数据截止日期：2019年10月31日；中位随访时间：10.6个月），乐伐替尼（体重≥60 kg患者的剂量为12 mg/天；体重<60 kg患者的剂量为8 mg/天）联合帕博利珠单抗200 mg，每3周一次，在一线不可切除肝细胞癌（uHCC）患者中显示出抗肿瘤活性和可控的安全性。本分析（更新数据截止日期：2021年3月31日）报告了额外17个月随访时间的疗效结果。
100例uHCC患者纳入主要分析（中位随访时间：27.6个月）。终点包括总生存期（OS）、研究者评估的无进展生存期（PFS）、客观缓解率（ORR）以及根据改良RECIST标准评估的缓解持续时间（DOR）。对3个月和9个月时最佳缓解的OS进行了标志性分析。还检测了帕博利珠单抗的抗药物抗体（ADA）及其浓度（截止日期：2020年8月7日）。
ORR为43.0%（95%CI 33.1 - 53.3%），中位DOR为17.1个月（95%CI 6.9 - 19.3个月）。中位PFS和OS分别为9.3个月（95%CI 7.4 - 9.8个月）和20.4个月（95%CI 14.4 - 25.9个月）。未检测到新出现的ADA。
结果显示，在一线治疗中，乐伐替尼联合帕博利珠单抗对uHCC患者具有持续的治疗效果。
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