Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
Cancer Res Commun. 2023 Jul 20;3(7):1312-1317. doi: 10.1158/2767-9764.CRC-23-0072. eCollection 2023 Jul.
Combination anti-PD-(L)1/CTLA-4 blockade is approved in patients with hepatocellular carcinoma (HCC) in the first-line setting or after sorafenib, but whether this treatment has efficacy after prior anti-PD-(L)1 therapy is unknown. We performed a multicenter retrospective review of patients with advanced HCC treated with ipilimumab plus nivolumab after prior anti-PD-(L)1 therapy, excluding patients with prior anti-CTLA-4 treatment. Of the 32 patients who met our inclusion criteria, prior anti-PD-(L)1 regimens included atezolizumab plus bevacizumab (50%, = 16), other anti-VEGF plus anti-PD-(L)1 combinations (31%, = 10), and anti-PD-(L)1 monotherapy (19%, = 6). The median number of prior systemic therapies was 2 (range, 1-8). The objective response rate with ipilimumab plus nivolumab by RECIST 1.1 was 22% [1 complete response (3%), 6 partial response (19%), 8 stable disease (25%), 16 progressive disease (50%), and 1 not evaluable (NE) (3%)], and objective response was associated with improved progression-free survival and overall survival. Immune-related adverse events were reported in 13 patients (41%), with no new safety signals. This study demonstrates that ipilimumab plus nivolumab has efficacy in patients with HCC who have received prior anti-PD-(L)1 therapy, suggesting that failure to respond to prior PD-(L)1 blockade should not preclude treatment with salvage ipilimumab plus nivolumab. Prospective studies are needed to define the optimal sequence of therapies.
Anti-PD-(L)1 containing regimens are the preferred first-line treatment for advanced HCC, but whether salvage with PD-(L)1/CTLA-4 blockade is effective in patients who have failed prior anti-PD-(L)1 therapy is unknown. Our study demonstrates that ipilimumab plus nivolumab has clinical activity in patients with advanced HCC previously treated with anti-PD-(L)1 therapy, supporting the continued use of this regimen in the late-line setting after prior anti-PD-(L)1 exposure.
联合抗 PD-(L)1/CTLA-4 阻断疗法已被批准用于一线治疗或索拉非尼治疗后的肝细胞癌 (HCC) 患者，但先前接受 PD-(L)1 治疗后该治疗方法是否有效尚不清楚。我们对先前接受 PD-(L)1 治疗后接受伊匹单抗联合纳武单抗治疗的晚期 HCC 患者进行了多中心回顾性研究，排除了先前接受 CTLA-4 治疗的患者。在符合我们纳入标准的 32 名患者中，先前的 PD-(L)1 方案包括阿替利珠单抗联合贝伐珠单抗（50%，n=16）、其他抗 VEGF 联合抗 PD-(L)1 联合治疗（31%，n=10）和 PD-(L)1 单药治疗（19%，n=6）。先前系统治疗的中位数为 2 种（范围，1-8）。根据 RECIST 1.1，伊匹单抗联合纳武单抗的客观缓解率为 22%[1 例完全缓解（3%），6 例部分缓解（19%），8 例稳定疾病（25%），16 例进展性疾病（50%），1 例无法评估（NE）（3%）]，客观缓解与无进展生存期和总生存期的改善相关。13 名患者（41%）报告了免疫相关不良事件，无新的安全信号。这项研究表明，先前接受 PD-(L)1 治疗的 HCC 患者接受伊匹单抗联合纳武单抗治疗具有疗效，这表明先前 PD-(L)1 阻断治疗失败不应排除 salvage 伊匹单抗联合纳武单抗治疗。需要前瞻性研究来确定最佳治疗方案顺序。
含 PD-(L)1 的方案是晚期 HCC 的首选一线治疗方法，但先前接受 PD-(L)1 治疗失败的患者是否可以通过 PD-(L)1/CTLA-4 阻断来进行挽救治疗尚不清楚。我们的研究表明，先前接受 PD-(L)1 治疗的晚期 HCC 患者使用伊匹单抗联合纳武单抗具有临床活性，支持在先前接受 PD-(L)1 暴露后晚期治疗线中继续使用该方案。
