Finn R S, Kudo M, Merle P, Meyer T, Qin S, Ikeda M, Xu R, Edeline J, Ryoo B-Y, Ren Z, Cheng A-L, Galle P R, Kaneko S, Kumada H, Kamble S, Norquist J M, Mody K, Wang A, Dubrovsky L, Llovet J M
Department of Medicine, Division of Hematology/Oncology, Geffen School of Medicine at UCLA, Los Angeles, USA.
Department of Gastroenterology and Hepatology, Kindai University, Faculty of Medicine, Osaka, Japan.
ESMO Open. 2025 May 27;10(6):105065. doi: 10.1016/j.esmoop.2025.105065.
Patients with advanced hepatocellular carcinoma (HCC) have a substantial symptom burden that affects their health-related quality of life (HRQoL). Assessing the impact of first-line regimens on HRQoL is essential to evaluate clinical benefit in addition to efficacy and safety in this setting.
LEAP-002 is a randomized phase III trial of lenvatinib plus pembrolizumab versus lenvatinib plus placebo as first-line treatment for participants with advanced HCC. Patient-reported outcomes (PROs) were prespecified exploratory endpoints assessed in all participants randomly assigned to treatment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 questionnaire (EORTC QLQ-C30), EORTC QLQ Hepatocellular Carcinoma 18-item module (EORTC QLQ-HCC18), and EuroQol 5-dimension, 5-level questionnaire (EQ-5D-5L) at baseline and throughout the trial. Median time to confirmed deterioration (TTD) in PROs was estimated using the Kaplan-Meier method. Least-squares mean change from baseline to week 27 (latest time point when completion and compliance rates were ≥60% and ≥80%, respectively) in PRO scores was assessed using a constrained longitudinal data analysis model. No formal hypotheses were tested.
The PRO population comprised 779 participants (lenvatinib plus pembrolizumab, n = 390; lenvatinib plus placebo, n = 389). Completion rates for all PRO assessments were >94% at baseline and >63% at week 27. Median TTD for EORTC QLQ-C30 global health status/quality-of-life score was 11.5 months [95% confidence interval (CI) 5.6 months-not reached] in the lenvatinib plus pembrolizumab group and 4.3 months (95% CI 3.5-5.5 months) in the lenvatinib plus placebo group (hazard ratio 0.80, 95% CI 0.65-0.98). TTD and least-squares mean change from baseline to week 27 were similar between treatment groups for EORTC QLQ-C30 scales, EORTC QLQ-HCC18 scores, and the EQ-5D-5L visual analog scale.
Adding pembrolizumab to lenvatinib, which is a current first-line option as a single agent, maintained HRQoL during the first-line treatment of participants with advanced HCC.
晚期肝细胞癌（HCC）患者存在严重的症状负担，这会影响他们的健康相关生活质量（HRQoL）。评估一线治疗方案对HRQoL的影响对于在此情况下除了评估疗效和安全性之外评估临床获益至关重要。
LEAP-002是一项随机III期试验，比较乐伐替尼联合帕博利珠单抗与乐伐替尼联合安慰剂作为晚期HCC患者的一线治疗。患者报告结局（PROs）是预先指定的探索性终点，在所有随机分配接受治疗的参与者中使用欧洲癌症研究与治疗组织生活质量问卷核心30问卷（EORTC QLQ-C30）、EORTC QLQ肝细胞癌18项模块（EORTC QLQ-HCC18）以及欧洲五维健康量表（EQ-5D-5L）在基线和整个试验过程中进行评估。使用Kaplan-Meier方法估计PROs中确认恶化的中位时间（TTD）。使用受限纵向数据分析模型评估从基线到第27周（完成率和依从率分别≥60%和≥80%的最新时间点）PRO分数的最小二乘均值变化。未检验正式假设。
PRO人群包括779名参与者（乐伐替尼联合帕博利珠单抗，n = 390；乐伐替尼联合安慰剂，n = 389）。所有PRO评估的完成率在基线时>94%，在第27周时>63%。在乐伐替尼联合帕博利珠单抗组中，EORTC QLQ-C30全球健康状况/生活质量评分的中位TTD为11.5个月[95%置信区间（CI）5.6个月 - 未达到]，在乐伐替尼联合安慰剂组中为4.3个月（95% CI 3.5 - 5.5个月）（风险比0.80，95% CI 0.65 - 0.98）。对于EORTC QLQ-C30量表、EORTC QLQ-HCC18评分和EQ-5D-5L视觉模拟量表，治疗组之间从基线到第27周的TTD和最小二乘均值变化相似。
在作为单药的当前一线选择乐伐替尼中添加帕博利珠单抗，在晚期HCC患者的一线治疗期间维持了HRQoL。
