Department of Immunology, Clinica Universidad de Navarra and CIBERONC, Pamplona, Spain.
Department of Medicine, University of Hong Kong, Hong Kong, China.
Ann Oncol. 2024 Jun;35(6):537-548. doi: 10.1016/j.annonc.2024.03.005. Epub 2024 May 22.
Nivolumab plus ipilimumab demonstrated promising clinical activity and durable responses in sorafenib-treated patients with advanced hepatocellular carcinoma (HCC) in the CheckMate 040 study at 30.7-month median follow-up. Here, we present 5-year results from this cohort.
Patients were randomized 1 : 1 : 1 to arm A [nivolumab 1 mg/kg plus ipilimumab 3 mg/kg Q3W (four doses)] or arm B [nivolumab 3 mg/kg plus ipilimumab 1 mg/kg Q3W (four doses)], each followed by nivolumab 240 mg Q2W, or arm C (nivolumab 3 mg/kg Q2W plus ipilimumab 1 mg/kg Q6W). The primary objectives were safety, tolerability, investigator-assessed objective response rate (ORR), and duration of response (DOR) per RECIST version 1.1.
A total of 148 patients were randomized across treatment arms. At 60-month minimum follow-up (62.6-month median follow-up), the ORR was 34% (n = 17), 27% (n = 13), and 29% (n = 14) in arms A, B, and C, respectively. The median DOR was 51.2 months [95% confidence interval (CI) 12.6 months-not estimable (NE)], 15.2 months (95% CI 7.1 months-NE), and 21.7 months (95% CI 4.2 months-NE), respectively. The median overall survival (OS) was 22.2 months (34/50; 95% CI 9.4-54.8 months) in arm A, 12.5 months (38/49; 95% CI 7.6-16.4 months) in arm B, and 12.7 months (40/49; 95% CI 7.4-30.5 months) in arm C; 60-month OS rates were 29%, 19%, and 21%, respectively. In an exploratory analysis of OS by response (6-month landmark), the median OS was meaningfully longer for responders versus nonresponders for all arms. No new safety signals were identified with longer follow-up. There were no new discontinuations due to immune-mediated adverse events since the primary analysis.
Consistent with the primary analysis, the arm A regimen of nivolumab plus ipilimumab continued to demonstrate clinically meaningful responses and long-term survival benefit, with no new safety signals in patients with advanced HCC following sorafenib treatment, further supporting its use as a second-line treatment in these patients.
在 CheckMate 040 研究中，纳武利尤单抗联合伊匹单抗在索拉非尼治疗的晚期肝细胞癌（HCC）患者中显示出有前景的临床活性和持久的缓解，中位随访时间为 30.7 个月。在此，我们报告了该队列的 5 年结果。
患者按 1:1:1 随机分配至 A 组（纳武利尤单抗 1 mg/kg 联合伊匹单抗 3 mg/kg，每 3 周一次[共 4 剂]）或 B 组（纳武利尤单抗 3 mg/kg 联合伊匹单抗 1 mg/kg，每 3 周一次[共 4 剂]），随后分别接受纳武利尤单抗 240 mg，每 2 周一次或 C 组（纳武利尤单抗 3 mg/kg 联合伊匹单抗 1 mg/kg，每 6 周一次）。主要目的是安全性、耐受性、研究者评估的客观缓解率（ORR）和根据 RECIST 版本 1.1 评估的缓解持续时间（DOR）。
共有 148 名患者在各治疗组中随机分组。在 60 个月的最小随访（中位随访 62.6 个月）时，A、B 和 C 组的 ORR 分别为 34%（n=17）、27%（n=13）和 29%（n=14）。中位 DOR 分别为 51.2 个月[95%置信区间（CI）12.6 个月-无法估计（NE）]、15.2 个月（95% CI 7.1 个月-NE）和 21.7 个月（95% CI 4.2 个月-NE）。A 组的中位总生存期（OS）为 22.2 个月（34/50；95% CI 9.4-54.8 个月），B 组为 12.5 个月（38/49；95% CI 7.6-16.4 个月），C 组为 12.7 个月（40/49；95% CI 7.4-30.5 个月）；60 个月的 OS 率分别为 29%、19%和 21%。在 OS 的一项基于 6 个月时间点的探索性分析中，所有组中，应答者的中位 OS 明显长于无应答者。随着随访时间的延长，没有发现新的安全性信号。与主要分析相比，自主要分析以来，没有因免疫介导的不良事件而导致新的停药。
与主要分析一致，纳武利尤单抗联合伊匹单抗的 A 组方案在索拉非尼治疗后晚期 HCC 患者中继续显示出有临床意义的缓解和长期生存获益，无新的安全性信号，进一步支持其在这些患者中作为二线治疗的应用。
