一线仑伐替尼联合帕博利珠单抗治疗肝细胞癌：3期LEAP-002试验日本患者的事后分析
First-Line Lenvatinib plus Pembrolizumab for Hepatocellular Carcinoma: Post hoc Analysis of Japanese Patients from the Phase 3 LEAP-002 Trial.
作者信息
Kudo Masatoshi, Ikeda Masafumi, Aikata Hiroshi, Numata Kazushi, Marusawa Hiroyuki, Hosaka Tetsuya, Kato Naoya, Kurosaki Masayuki, Morimoto Manabu, Yamashita Tatsuya, Koga Hironori, Masaki Tsutomu, Yatsuzuka Naoyoshi, Suzuki Masato, Nagao Satoshi, Kaneko Shuichi, Kumada Hiromitsu
机构信息
Kindai University Hospital, Osaka, Japan.
National Cancer Center Hospital East, Kashiwa, Japan.
出版信息
Liver Cancer. 2024 Nov 14;14(4):365-377. doi: 10.1159/000542572. eCollection 2025 Aug.
INTRODUCTION
The phase 3 LEAP-002 study (NCT03713593) of advanced hepatocellular carcinoma (HCC) suggested improved antitumor activity of lenvatinib plus pembrolizumab versus lenvatinib alone with manageable safety, although overall survival (OS) and progression-free survival (PFS) did not reach prespecified statistical significance. This post hoc analysis assessed efficacy and safety in Japanese patients.
METHODS
Patients with advanced HCC without prior systemic treatment were randomly assigned 1:1 to receive 8 mg (body weight <60 kg) or 12 mg (body weight ≥60 kg) oral lenvatinib once daily plus 200 mg intravenous pembrolizumab or placebo every 3 weeks for up to 35 cycles. Dual primary end points were OS and PFS per RECIST v1.1 by blinded independent central review (BICR). Secondary end points were objective response rate, disease control rate, duration of response, and time to progression per RECIST v1.1 by BICR and safety.
RESULTS
Overall, 80 patients were enrolled in Japan (lenvatinib plus pembrolizumab, = 39; lenvatinib plus placebo, = 41). Median time from randomization to database cutoff (June 21, 2022) was 34.1 months (range: 26.9-39.6). Median OS was 31.4 months (95% CI: 21.2- not reached) for lenvatinib plus pembrolizumab and 21.4 months (95% CI: 14.4-25.4) for lenvatinib plus placebo (hazard ratio [HR] = 0.55 [95% CI: 0.31-0.96]). Median PFS for lenvatinib plus pembrolizumab was 10.4 months (95% CI: 6.2-18.5) and 6.5 months (95% CI: 6.0-8.3) for lenvatinib plus placebo (HR = 0.54 [95% CI: 0.32-0.90]). Grade 3 or 4 treatment-related adverse events occurred in 26 patients (67%) in the lenvatinib plus pembrolizumab group and 24 patients (59%) in the lenvatinib plus placebo group.
CONCLUSION
In Japanese patients enrolled in LEAP-002, findings were consistent with the global population where OS and PFS trended toward improvement; a similar safety profile was observed.
引言
晚期肝细胞癌（HCC）的3期LEAP-002研究（NCT03713593）表明，与单用乐伐替尼相比，乐伐替尼联合帕博利珠单抗具有更好的抗肿瘤活性，安全性可控，尽管总生存期（OS）和无进展生存期（PFS）未达到预先设定的统计学显著性。这项事后分析评估了日本患者的疗效和安全性。
方法
未接受过全身治疗的晚期HCC患者按1:1随机分组，分别接受8毫克（体重<60千克）或12毫克（体重≥60千克）口服乐伐替尼，每日一次，加每3周静脉注射200毫克帕博利珠单抗或安慰剂，最多35个周期。双重主要终点是根据实体瘤疗效评价标准（RECIST）v1.1，由盲法独立中央审查（BICR）评估的OS和PFS。次要终点是根据RECIST v1.1，由BICR评估的客观缓解率、疾病控制率、缓解持续时间和进展时间以及安全性。
结果
总体而言，日本有80名患者入组（乐伐替尼加帕博利珠单抗组，n = 39；乐伐替尼加安慰剂组，n = 41）。从随机分组到数据库截止日期（2022年6月21日）的中位时间为34.1个月（范围：26.9 - 39.6个月）。乐伐替尼加帕博利珠单抗组的中位OS为31.4个月（95%置信区间：21.2 - 未达到），乐伐替尼加安慰剂组为21.4个月（95%置信区间：14.4 - 25.4个月）（风险比[HR]=0.55[95%置信区间：0.31 - 0.96]）。乐伐替尼加帕博利珠单抗组的中位PFS为10.4个月（95%置信区间：6.2 - 18.5个月），乐伐替尼加安慰剂组为6.5个月（95%置信区间：6.0 - 8.3个月）（HR = 0.54[95%置信区间：0.32 - 0.90]）。乐伐替尼加帕博利珠单抗组有26名患者（67%）发生3级或4级治疗相关不良事件，乐伐替尼加安慰剂组有24名患者（59%）发生。
结论
在LEAP-002研究入组的日本患者中，研究结果与全球人群一致，OS和PFS有改善趋势；观察到相似的安全性概况。
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