Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX.
J Clin Oncol. 2021 Feb 20;39(6):599-607. doi: 10.1200/JCO.20.00605. Epub 2020 Oct 30.
Metastatic uveal melanoma has poor overall survival (OS) and no approved systemic therapy options. Studies of single-agent immunotherapy regimens have shown minimal benefit. There is the potential for improved responses with the use of combination immunotherapy.
We conducted a phase II study of nivolumab with ipilimumab in patients with metastatic uveal melanoma. Any number of prior treatments was permitted. Patients received nivolumab 1 mg/kg and ipilimumab 3 mg/kg for four cycles, followed by nivolumab maintenance therapy for up to 2 years. The primary outcome of the study was overall response rate (ORR) as determined by RECIST 1.1 criteria. Progression-free survival (PFS), OS, and adverse events were also assessed.
Thirty-five patients were enrolled, and 33 patients were evaluable for efficacy. The ORR was 18%, including one confirmed complete response and five confirmed partial responses. The median PFS was 5.5 months (95% CI, 3.4 to 9.5 months), and the median OS was 19.1 months (95% CI, 9.6 months to NR). Forty percent of patients experienced a grade 3-4 treatment-related adverse event.
The combination regimen of nivolumab plus ipilimumab demonstrates activity in metastatic uveal melanoma, with deep and sustained confirmed responses.
转移性葡萄膜黑色素瘤的总体存活率（OS）较差，且尚无批准的系统治疗选择。单药免疫治疗方案的研究显示出最小的益处。联合免疫疗法有可能提高反应率。
我们对转移性葡萄膜黑色素瘤患者进行了纳武单抗联合伊匹单抗的 II 期研究。允许患者接受任意数量的既往治疗。患者接受纳武单抗 1 mg/kg 和伊匹单抗 3 mg/kg 治疗四个周期，随后接受纳武单抗维持治疗长达 2 年。该研究的主要终点是根据 RECIST 1.1 标准确定的总体缓解率（ORR）。还评估了无进展生存期（PFS）、OS 和不良事件。
共纳入 35 例患者，33 例患者可评估疗效。ORR 为 18%，包括 1 例确认的完全缓解和 5 例确认的部分缓解。中位 PFS 为 5.5 个月（95%CI，3.4 至 9.5 个月），中位 OS 为 19.1 个月（95%CI，9.6 个月至不可评估）。40%的患者发生 3-4 级治疗相关不良事件。
纳武单抗联合伊匹单抗的联合治疗方案在转移性葡萄膜黑色素瘤中显示出活性，具有深度和持续的确认缓解。
