Early discontinuation of PD-1 blockade upon achieving a complete or partial response in patients with advanced melanoma: the multicentre prospective Safe Stop trial

BMC Cancer

A. J. ten Tije¹  R. S. van Rijn²  D. Piersma³  G. Vreugdenhil⁴  F. W. P. J. van den Berkmortel⁵  A. J. M. van den Eertwegh⁶  S. Sleijfer⁷  K. de Joode⁷  E. Oomen-de Hoop⁷  A. A. M. van der Veldt⁸  E. E. A. P. Mulder⁹  J. W. B. de Groot^1,10  E. Kapiteijn^1,11  M. J. B. Aarts^1,12  J. B. A. G. Haanen^1,13  M. J. Boers-Sonderen^1,14  G. A. P. Hospers^1,15  K. P. M. Suijkerbuijk^1,16  P. Rutkowski^1,17  S. Litière^1,18  M. G. Franken^1,19  B. Ryll^2,20 

[1] Department of Internal Medicine, Amphia Hospital, Breda, The Netherlands;Department of Internal Medicine, Medical Centre Leeuwarden, Leeuwarden, The Netherlands;Department of Internal Medicine, Medisch Spectrum Twente, Enschede, The Netherlands;Department of Internal Medicine, Máxima Medical Centre, Veldhoven, The Netherlands;Department of Internal Medicine, Zuyderland Medical Centre, Sittard-Geleen, The Netherlands;Department of Medical Oncology, Amsterdam University Medical Centre – location VU, Amsterdam, The Netherlands;Department of Medical Oncology, Erasmus Medical Centre Cancer Institute, Rotterdam, The Netherlands;Department of Medical Oncology, Erasmus Medical Centre Cancer Institute, Rotterdam, The Netherlands;Department of Radiology & Nuclear Medicine, Erasmus Medical Centre Cancer Institute, Rotterdam, The Netherlands;Department of Medical Oncology, Erasmus Medical Centre Cancer Institute, Rotterdam, The Netherlands;Department of Surgical Oncology, Erasmus Medical Centre Cancer Institute, Rotterdam, The Netherlands;Department of Medical Oncology, Isala Oncological Centre, Zwolle, The Netherlands;Department of Medical Oncology, Leiden University Medical Centre, Leiden, The Netherlands;Department of Medical Oncology, Maastricht University Medical Centre +, Maastricht, The Netherlands;Department of Medical Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands;Department of Medical Oncology, Radboud University Medical Centre, Nijmegen, The Netherlands;Department of Medical Oncology, University Medical Centre Groningen, Groningen, The Netherlands;Department of Medical Oncology, University Medical Centre Utrecht Cancer Centre, Utrecht, The Netherlands;Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland;European Organisation for Research and Treatment of Cancer (EORTC), Brussels, Belgium;Institute for Medical Technology Assessment, Erasmus School of Health Policy & Management, Erasmus University Rotterdam, Rotterdam, The Netherlands;Melanoma Patient Network Europe, Uppsala, Sweden;

关键词: Melanoma;    Advanced and metastatic;    PD-1 blockade;    Response (complete or partial);    Health-related quality of life;   

DOI  :  10.1186/s12885-021-08018-w

来源: Springer

【 摘 要 】

BackgroundThe 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.MethodsThe 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.DiscussionFrom 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.Trial registrationThe 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.

【 授权许可】

CC BY