Department of Medical Oncology, Erasmus Medical Centre Cancer Institute, Rotterdam, The Netherlands.
Department of Surgical Oncology, Erasmus Medical Centre Cancer Institute, Rotterdam, The Netherlands.
BMC Cancer. 2021 Mar 25;21(1):323. doi: 10.1186/s12885-021-08018-w.
The introduction of programmed cell death protein 1 (PD-1) blockers (i.e. nivolumab and pembrolizumab) has significantly improved the prognosis of patients with advanced melanoma. However, the long treatment duration (i.e. two years or longer) has a high impact on patients and healthcare systems in terms of (severe) toxicity, health-related quality of life (HRQoL), resource use, and healthcare costs. While durable tumour responses have been observed and PD-1 blockade is discontinued on an individual basis, no consensus has been reached on the optimal treatment duration. The objective of the Safe Stop trial is to evaluate whether early discontinuation of first-line PD-1 blockade is safe in patients with advanced and metastatic melanoma who achieve a radiological response.
The Safe Stop trial is a nationwide, multicentre, prospective, single-arm, interventional study in the Netherlands. A total of 200 patients with advanced and metastatic cutaneous melanoma and a confirmed complete response (CR) or partial response (PR) according to response evaluation criteria in solid tumours (RECIST) v1.1 will be included to early discontinue first-line monotherapy with nivolumab or pembrolizumab. The primary objective is the rate of ongoing responses at 24 months after discontinuation of PD-1 blockade. Secondary objectives include best overall and duration of response, need and outcome of rechallenge with PD-1 blockade, and changes in (serious) adverse events and HRQoL. The impact of treatment discontinuation on healthcare resource use, productivity losses, and hours of informal care will also be assessed. Results will be compared to those from patients with CR or PR who completed 24 months of treatment with PD-1 blockade and had an ongoing response at treatment discontinuation. It is hypothesised that it is safe to early stop first-line nivolumab or pembrolizumab at confirmed tumour response while improving HRQoL and reducing costs.
From a patient, healthcare, and economic perspective, shorter treatment duration is preferred and overtreatment should be prevented. If early discontinuation of first-line PD-1 blockade appears to be safe, early discontinuation of PD-1 blockade may be implemented as the standard of care in a selected group of patients.
The Safe Stop trial has been registered in the Netherlands Trial Register (NTR), Trial NL7293 (old NTR ID: 7502), https://www.trialregister.nl/trial/7293 . Date of registration September 30, 2018.
程序性死亡蛋白 1（PD-1）抑制剂（如纳武利尤单抗和帕博利珠单抗）的引入显著改善了晚期黑色素瘤患者的预后。然而，由于（严重）毒性、健康相关生活质量（HRQoL）、资源利用和医疗保健成本等方面的原因，长期治疗（即 2 年或更长时间）对患者和医疗保健系统具有重大影响。虽然已经观察到持久的肿瘤缓解，并且根据实体瘤反应评估标准（RECIST）v1.1 基于个体情况停用 PD-1 阻断剂，但尚未就最佳治疗持续时间达成共识。Safe Stop 试验的目的是评估在达到影像学缓解的晚期和转移性黑色素瘤患者中，早期停止一线 PD-1 阻断治疗是否安全。
Safe Stop 试验是一项在荷兰进行的全国性、多中心、前瞻性、单臂、干预性研究。总共将纳入 200 名患有晚期和转移性皮肤黑色素瘤的患者，这些患者的完全缓解（CR）或部分缓解（PR）根据实体瘤反应评估标准（RECIST）v1.1 得到确认，他们将接受早期停止一线纳武利尤单抗或帕博利珠单抗单药治疗。主要目标是在 PD-1 阻断治疗停止后 24 个月时持续反应的发生率。次要目标包括最佳总反应和反应持续时间、再次使用 PD-1 阻断治疗的需求和结果，以及（严重）不良事件和 HRQoL 的变化。还将评估治疗中断对医疗资源利用、生产力损失和非正式护理时间的影响。结果将与完成 24 个月 PD-1 阻断治疗且在治疗停止时仍有持续反应的 CR 或 PR 患者进行比较。假设在确认肿瘤反应时，早期停止一线 nivolumab 或 pembrolizumab 是安全的，同时可以提高 HRQoL 并降低成本。
从患者、医疗保健和经济角度来看，较短的治疗时间是首选，应避免过度治疗。如果早期停止一线 PD-1 阻断治疗似乎是安全的，那么早期停止 PD-1 阻断治疗可能会作为选定患者群体的标准治疗方法实施。
Safe Stop 试验已在荷兰试验注册处（NTR）注册，试验 NL7293（旧 NTR ID：7502），https://www.trialregister.nl/trial/7293。注册日期 2018 年 9 月 30 日。
