Scientific department, Dutch Institute for Clincal Auditing.
Departments of Department of Medical Oncology, Leiden University Medical Centre.
J Immunother. 2020 Oct;43(8):256-264. doi: 10.1097/CJI.0000000000000334.
The efficacy of anti-programmed death-1 (PD-1) monotherapy for advanced melanoma has been established, but it is unknown to what extent patients benefit in the real world. In this observational study with nationwide population-based data from the Dutch Melanoma Treatment Registry, we analyzed real-world outcomes of first-line anti-PD-1 monotherapy in advanced melanoma patients diagnosed in 2015 to 2016. Overall survival (OS) was estimated with the Kaplan-Meier method. Competing risks analysis was used to estimate probabilities for second-line treatment, with death as competing risk. With a Cox model, the association of factors with OS was estimated. Patients who received anti-PD-1 monotherapy (n=550) had a median age of 65 years and 502 (95%) patients had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1, 383 (70%) had normal lactate dehydrogenase (LDH), 370 (67%) had stage IV-M1c disease, and in 441 (81%), brain metastases were absent. The median OS was 24 months [95% confidence interval (CI): 20-30 mo]. The median OS of patients normally eligible for phase III trial participation was 31 months (95% CI: 23-not estimable). The BRAF mutation was associated with superior OS. ECOG PS of ≥1, symptomatic brain metastases, and liver metastases were associated with inferior OS and, together with elevated LDH, with death before second-line treatment. Patients with a complete response had a 2-year OS probability from first reported complete response of 92% (95% CI: 86%-99%). Real-world advanced melanoma patients in the Netherlands have benefitted from anti-PD-1 monotherapy. ECOG PS ≥1, symptomatic brain metastasis, liver metastasis, and elevated LDH are important prognostic factors for survival. The additional information that this study provides could help to improve more effective use in the real world.
抗程序性死亡-1（PD-1）单药治疗晚期黑色素瘤的疗效已得到证实，但在真实世界中患者受益的程度尚不清楚。在这项使用荷兰黑色素瘤治疗登记处全国人群数据的观察性研究中，我们分析了 2015 年至 2016 年诊断为晚期黑色素瘤的一线抗 PD-1 单药治疗的真实世界结果。采用 Kaplan-Meier 法估计总生存期（OS）。采用竞争风险分析估计二线治疗的概率，以死亡为竞争风险。使用 Cox 模型估计与 OS 相关的因素。接受抗 PD-1 单药治疗的患者（n=550）中位年龄为 65 岁，502 例（95%）患者的东部合作肿瘤组表现状态（ECOG PS）为 0-1，383 例（70%）乳酸脱氢酶（LDH）正常，370 例（67%）为 IV 期 M1c 期疾病，441 例（81%）无脑转移。中位 OS 为 24 个月[95%置信区间（CI）：20-30 mo]。正常符合 III 期试验参与条件的患者中位 OS 为 31 个月（95% CI：23-无法估计）。BRAF 突变与 OS 改善相关。ECOG PS≥1、有症状脑转移和肝转移与 OS 降低相关，与 LDH 升高一起与二线治疗前死亡相关。完全缓解患者从首次报告完全缓解的 2 年 OS 概率为 92%（95% CI：86%-99%）。荷兰的晚期黑色素瘤真实世界患者从抗 PD-1 单药治疗中获益。ECOG PS≥1、有症状脑转移、肝转移和 LDH 升高是生存的重要预后因素。本研究提供的额外信息有助于改善真实世界中的有效应用。
