Division of Hematology-Oncology, University of California, Los Angeles, Santa Monica, California.
Jonsson Comprehensive Cancer Center, Los Angeles, California.
Clin Cancer Res. 2022 Jan 1;28(1):84-94. doi: 10.1158/1078-0432.CCR-21-0878. Epub 2021 Aug 18.
Most gastrointestinal stromal tumors (GIST) are driven by KIT/PDGFRa mutations. Tyrosine kinase inhibitor benefit is progressively less after imatinib failure. This phase II trial analyzed the efficacy of nivolumab (N) or nivolumab + ipilimumab (N + I) in patients with refractory GIST.
Patients with advanced/metastatic GIST refractory to at least imatinib were randomized 1:1 in a noncomparative, parallel group, unblinded phase II trial of N (240 mg every 2 weeks) or N + I (240 mg every 2 weeks + 1 mg/kg every 6 weeks). The primary endpoint was the objective response rate of N alone or N+I by RECIST 1.1 in the intent-to-treat population.
A total of 36 patients with a median of 3 (1-6) prior lines of therapies were enrolled. Ten of 19 (52.6%) patients had stable disease (SD) for a clinical benefit rate (CBR) of 52.6% in the N arm and the median progression-free survival (PFS) was 11.7 weeks [95% confidence interval (CI), 7.0-17.4]. In the N+I arm, 1 of 16 (6.7%) patients had a complete response (CR) and 4/16 (25.0%) had SD for a CBR of 31.3% and a median PFS of 8.3 weeks (95% CI, 5.6-22.2). The 4- and 6-month PFS were 42.1% and 26.3%, respectively for N, and 31.3% and 18.8%, respectively for N+I. The most common adverse events (AE) attributed to N and N+I were fatigue: 13.9% and 22.2%, respectively. There were nine total attributable grade 3-4 AEs.
The primary endpoint of response rate > 15% was not observed for N or N + I. In a heavily pretreated GIST population, responses and long-term disease control with both N and N+I were observed. No new safety signals have been observed.
大多数胃肠道间质瘤（GIST）受 KIT/PDGFRa 突变驱动。在伊马替尼耐药后，酪氨酸激酶抑制剂的获益逐渐减少。本Ⅱ期试验分析了纳武利尤单抗（N）或纳武利尤单抗+伊匹单抗（N+I）在难治性 GIST 患者中的疗效。
至少接受过伊马替尼治疗的晚期/转移性 GIST 患者，按照 1:1 比例，在非比较、平行组、开放标签的Ⅱ期 N（240 mg，每 2 周）或 N+I（240 mg，每 2 周+1 mg/kg，每 6 周）组中进行随机分组。主要终点为意向治疗人群中，按 RECIST 1.1 标准，N 或 N+I 的客观缓解率。
共纳入 36 例患者，中位治疗线数为 3（1-6）线。N 组中，19 例患者中有 10 例（52.6%）疾病稳定（SD），临床获益率（CBR）为 52.6%，中位无进展生存期（PFS）为 11.7 周[95%置信区间（CI），7.0-17.4]。在 N+I 组中，16 例患者中有 1 例（6.7%）达完全缓解（CR），4/16 例（25.0%）SD，CBR 为 31.3%，中位 PFS 为 8.3 周[95%CI，5.6-22.2]。4 个月和 6 个月的 PFS 分别为 N 组的 42.1%和 26.3%，N+I 组的 31.3%和 18.8%。最常见的与 N 和 N+I 相关的不良事件（AE）为疲劳：分别为 13.9%和 22.2%。共有 9 例完全归因于 3-4 级 AE。
N 或 N+I 的缓解率>15%的主要终点未达到。在治疗线数较多的 GIST 人群中，观察到 N 和 N+I 都有应答和长期疾病控制。未观察到新的安全性信号。
