伊匹单抗单药治疗预处理的晚期黑色素瘤患者的疗效和安全性：一项多中心单臂 II 期研究。

Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: a multicenter single-arm phase II study.

机构信息

The Angeles Clinic and Research Institute, Santa Monica, CA, USA.

Division of Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena.

出版信息

Ann Oncol. 2010 Aug;21(8):1712-1717. doi: 10.1093/annonc/mdq013. Epub 2010 Feb 10.

DOI:10.1093/annonc/mdq013

PMID:20147741

Abstract

BACKGROUND

This phase II study evaluated the safety and activity of ipilimumab, a fully human mAb that blocks cytotoxic T-lymphocyte antigen-4, in patients with advanced melanoma.

PATIENTS AND METHODS

Patients with previously treated, unresectable stage III/stage IV melanoma received 10 mg/kg ipilimumab every 3 weeks for four cycles (induction) followed by maintenance therapy every 3 months. The primary end point was best overall response rate (BORR) using modified World Health Organization (WHO) criteria. We also carried out an exploratory analysis of proposed immune-related response criteria (irRC).

RESULTS

BORR was 5.8% with a disease control rate (DCR) of 27% (N = 155). One- and 2-year survival rates (95% confidence interval) were 47.2% (39.5% to 55.1%) and 32.8% (25.4% to 40.5%), respectively, with a median overall survival of 10.2 months (7.6-16.3). Of 43 patients with disease progression by modified WHO criteria, 12 had disease control by irRC (8% of all treated patients), resulting in a total DCR of 35%. Adverse events (AEs) were largely immune related, occurring mainly in the skin and gastrointestinal tract, with 19% grade 3 and 3.2% grade 4. Immune-related AEs were manageable and generally reversible with corticosteroids.

CONCLUSION

Ipilimumab demonstrated clinical activity with encouraging long-term survival in a previously treated advanced melanoma population.

摘要

背景

本 II 期研究评估了 ipilimumab（一种完全人源化单克隆抗体，可阻断细胞毒性 T 淋巴细胞抗原-4）在晚期黑色素瘤患者中的安全性和疗效。

患者和方法

先前接受过治疗、不可切除的 III/IV 期黑色素瘤患者接受每 3 周 10mg/kg 的 ipilimumab 治疗，共 4 个周期（诱导期），然后每 3 个月进行维持治疗。主要终点是根据改良的世界卫生组织（WHO）标准评估的最佳总体缓解率（BORR）。我们还对提出的免疫相关反应标准（irRC）进行了探索性分析。

结果

BORR 为 5.8%，疾病控制率（DCR）为 27%（N=155）。1 年和 2 年的生存率（95%置信区间）分别为 47.2%（39.5%至 55.1%）和 32.8%（25.4%至 40.5%），中位总生存期为 10.2 个月（7.6-16.3）。根据改良的 WHO 标准，43 例疾病进展的患者中，有 12 例根据 irRC 疾病得到控制（所有治疗患者的 8%），总 DCR 为 35%。不良事件（AE）主要与免疫相关，主要发生在皮肤和胃肠道，3.2%为 3 级，19%为 4 级。免疫相关 AE 可通过皮质类固醇治疗控制且通常是可逆的。