Supplementary Material for: First-Line Lenvatinib Plus Pembrolizumab for Hepatocellular Carcinoma: Post Hoc Analysis of Japanese Patients From the Phase 3 LEAP-002 Trial

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, n = 39; lenvatinib plus placebo, n = 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：针对晚期肝细胞癌（hepatocellular carcinoma, HCC）的Ⅲ期LEAP-002研究（NCT03713593）结果显示，仑伐替尼联合帕博利珠单抗对比单用仑伐替尼具有更优的抗肿瘤活性，且安全性可控，不过两组的总生存期（overall survival, OS）与无进展生存期（progression-free survival, PFS）未达到预设的统计学显著性标准。本事后分析针对日本患者的疗效与安全性进行了评估。
方法：将既往未接受过全身治疗的晚期肝细胞癌患者按1:1随机分组，分别接受每日一次口服仑伐替尼（体重＜60kg者予8mg，体重≥60kg者予12mg）联合每3周静脉输注200mg帕博利珠单抗或安慰剂的治疗，最多持续35个周期。双主要终点为由盲法独立中央审查（blinded independent central review, BICR）依据实体瘤疗效评价标准v1.1（RECIST v1.1）评估的总生存期与无进展生存期。次要终点包括由BICR依据RECIST v1.1评估的客观缓解率、疾病控制率、缓解持续时间及至疾病进展时间，以及安全性。
结果：日本地区共入组80例患者（仑伐替尼联合帕博利珠单抗组n=39；仑伐替尼联合安慰剂组n=41）。从随机分组至数据库锁库（2022年6月21日）的中位时间为34.1个月（范围：26.9~39.6）。仑伐替尼联合帕博利珠单抗组的中位总生存期为31.4个月（95%置信区间：21.2~未达到），仑伐替尼联合安慰剂组为21.4个月（95%置信区间：14.4~25.4）（风险比[HR]=0.55，95%置信区间：0.31~0.96）。仑伐替尼联合帕博利珠单抗组的中位无进展生存期为10.4个月（95%置信区间：6.2~18.5），仑伐替尼联合安慰剂组为6.5个月（95%置信区间：6.0~8.3）（HR=0.54，95%置信区间：0.32~0.90）。仑伐替尼联合帕博利珠单抗组中26例患者（67%）发生3级或4级治疗相关不良事件，仑伐替尼联合安慰剂组为24例患者（59%）。
结论：在纳入LEAP-002研究的日本患者中，研究结果与全球人群一致，总生存期与无进展生存期均呈改善趋势；两组的安全性特征相似。