Historically, patients with metastatic renal cell carcinoma (mRCC) have been offered upfront cytoreductive nephrectomy (CN) followed by systemic therapy. Currently, CN is no longer the standard of care (SOC) based on the randomised phase 3 CARMENA study performed in the vascular endothelial growth factor receptor tyrosine kinase inhibitor era. With the advent of immune checkpoint inhibitor (ICI) combination therapy in first line, the role of CN needs to be reassessed. There is indirect evidence from small retrospective series that deferred CN after ICI combination therapy may lead to better outcomes. To reassess the role of CN, we designed PrimerX, a randomised controlled trial following the Trial within Cohorts (TwiCs) study design. The primary objective of this study is to re-evaluate the benefit of deferred local treatment in the current era of immunotherapy.
This PrimerX study has been designed as a TwiCs study within the Dutch Prospective Renal Cell Carcinoma (PRO-RCC) cohort. The PRO-RCC cohort includes patients with mRCC and nonmetastatic RCC, and has been set up for prospective collection of long-term clinical data and as an infrastructure for initiating TwiCs studies. The PrimerX TwiCs trial follows a Bayesian adaptive multistage design to allow for early discontinuation due to futility or efficacy. PrimerX has appropriate ethics approval and is registered at clinical.trials.gov (NCT05941169).
The primary clinical endpoint is overall survival, defined as the time from randomisation to death from any cause. The secondary endpoint is the objective response rate within the primary tumour prior to local therapy, as assessed by a computed tomography scan.
A maximum of 700 patients with synchronous mRCC and absence of progression at metastatic sites following at least 6 mo of standard first-line ICI combination therapy will be assigned randomly to receive local treatment of the primary tumour (experimental arm) or SOC (control arm). The experimental intervention consists of (partial) CN, any form of ablative local therapy, or magnetic resonance imaging guided ablative stereotactic radiotherapy, performed within 6 mo and 1.5 yr after the start of systemic treatment.
European urology open science. 2024 Oct 14*** epublish ***
Orlane Figaroa, Patricia Zondervan, Rob Kessels, Johannes Berkhof, Maureen Aarts, Paul Hamberg, Maartje Los, Djura Piersma, Bart Rikhof, Britt Suelmann, Metin Tascilar, Astrid van der Veldt, Paul Verhagen, Hans Westgeest, Hilin Yildirim, Axel Bex, Adriaan Bins
Department of Medical Oncology, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, The Netherlands., Department of Urology, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, The Netherlands., Julius Center for Health Sciences and Primary Care, Department of Data Science and Biostatistics, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands., Department of Epidemiology and Data Science, Amsterdam UMC location Vrije Universiteit, Amsterdam, The Netherlands., Department of Medical Oncology, Maastricht University Medical Centre, Maastricht, The Netherlands., Department of Internal Medicine, Franciscus Gasthuis, Vlietland, Rotterdam/Schiedam, The Netherlands., Department of Medical Oncology, St. Antonius Ziekenhuis, Nieuwegein/Utrecht, The Netherlands., Department of Medical Oncology, Medical Spectrum Twente, Enschede, The Netherlands., Department of Medical Oncology, Leeuwarden Medical Center, Leeuwarden, The Netherlands., Department of Medical Oncology, Utrecht University Medical Centre, Utrecht, The Netherlands., Department of Medical Oncology, Isala Medical Centre, Zwolle, The Netherlands., Department of Medical Oncology, Erasmus Medical Center, Rotterdam, The Netherlands., Department of Urology, Erasmus Medical Center, Rotterdam, The Netherlands., Department of Medical Oncology, Amphia Medical Centre, Breda, The Netherlands., Department of Urology, Antoni van Leeuwenhoek Hospital-The Netherlands Cancer Institute, Amsterdam, The Netherlands.