Zimmer Lisa, Vaubel Julia, Mohr Peter, Hauschild Axel, Utikal Jochen, Simon Jan, Garbe Claus, Herbst Rudolf, Enk Alexander, Kämpgen Eckhart, Livingstone Elisabeth, Bluhm Leonie, Rompel Rainer, Griewank Klaus G, Fluck Michael, Schilling Bastian, Schadendorf Dirk
Department of Dermatology, University Hospital, University Duisburg-Essen, Essen, Germany.
Department of Dermatology, Buxtehude, Germany.
PLoS One. 2015 Mar 11;10(3):e0118564. doi: 10.1371/journal.pone.0118564. eCollection 2015.
Up to 50% of patients with uveal melanoma (UM) develop metastatic disease with limited treatment options. The immunomodulating agent ipilimumab has shown an overall survival (OS) benefit in patients with cutaneous metastatic melanoma in two phase III trials. As patients with UM were excluded in these studies, the Dermatologic Cooperative Oncology Group (DeCOG) conducted a phase II to assess the efficacy and safety of ipilimumab in patients with metastatic UM.
We undertook a multicenter phase II study in patients with different subtypes of metastatic melanoma. Here we present data on patients with metastatic UM (pretreated and treatment-naïve) who received up to four cycles of ipilimumab administered at a dose of 3 mg/kg in 3 week intervals. Tumor assessments were conducted at baseline, weeks 12, 24, 36 and 48 according to RECIST 1.1 criteria. Adverse events (AEs), including immune-related AEs were graded according to National Cancer Institute Common Toxicity Criteria (CTC) v.4.0. Primary endpoint was the OS rate at 12 months.
Forty five pretreated (85%) and eight treatment-naïve (15%) patients received at least one dose of ipilimumab. 1-year and 2-year OS rates were 22% and 7%, respectively. Median OS was 6.8 months (95% CI 3.7-8.1), median progression-free survival 2.8 months (95% CI 2.5-2.9). The disease control rate at weeks 12 and 24 was 47% and 21%, respectively. Sixteen patients had stable disease (47%), none experienced partial or complete response. Treatment-related AEs were observed in 35 patients (66%), including 19 grade 3-4 events (36%). One drug-related death due to pancytopenia was observed.
Ipilimumab has very limited clinical activity in patients with metastatic UM. Toxicity was manageable when treated as per protocol-specific guidelines.
ClinicalTrials.gov NCT01355120.
高达50%的葡萄膜黑色素瘤（UM）患者会发生转移性疾病，且治疗选择有限。免疫调节剂伊匹单抗在两项III期试验中已显示出对皮肤转移性黑色素瘤患者有总生存期（OS）获益。由于这些研究排除了UM患者，皮肤肿瘤协作肿瘤学组（DeCOG）开展了一项II期试验，以评估伊匹单抗对转移性UM患者的疗效和安全性。
我们对不同亚型的转移性黑色素瘤患者进行了一项多中心II期研究。在此，我们呈现接受最多四个周期伊匹单抗治疗患者的数据，伊匹单抗剂量为3mg/kg，每3周给药一次，这些患者包括预处理患者和初治患者。根据RECIST 1.1标准在基线、第12周、24周、36周和48周进行肿瘤评估。不良事件（AE），包括免疫相关AE，根据美国国立癌症研究所通用毒性标准（CTC）v.4.0进行分级。主要终点是12个月时的OS率。
45例预处理患者（85%）和8例初治患者（15%）接受了至少一剂伊匹单抗。1年和2年OS率分别为22%和7%。中位OS为6.8个月（95%CI 3.7 - 8.1），中位无进展生存期为2.8个月（95%CI 2.5 - 2.9）。第12周和24周时的疾病控制率分别为47%和21%。16例患者病情稳定（47%），无患者出现部分或完全缓解。35例患者（66%）观察到治疗相关AE，包括19例3 - 4级事件（36%）。观察到1例因全血细胞减少导致的药物相关死亡。
伊匹单抗对转移性UM患者的临床活性非常有限。按照方案特定指南进行治疗时，毒性是可控的。
ClinicalTrials.gov NCT01355120
