Optimal treatment duration in metastatic renal cell carcinoma patients responding to immune checkpoint inhibitors: should we treat beyond two years?

Authors

  • Alexander Decruyenaere Department of Medical Oncology, Ghent University Hospital, Gent, Belgium
  • Gennigens Christine Department of Medical Oncology, CHU Liège, Liège, Belgium
  • Rottey Sylvie Department of Medical Oncology, Ghent University Hospital, Gent, Belgium
  • Laenen Annouschka Biostatistics and Statistical Bioinformatics Center, Leuven, Belgium
  • Emmanuel Seront Oncologie Médicale, UCL St-Luc, Bruxelles, Belgium
  • Els Everaert Medische Oncologie, VITAZ, St Niklaas, Belgium
  • Philip R Debruyne Kortrijk Cancer Centre, General Hospital AZ Groeninge, Kortrijk, Belgium; Medical Technology Research Centre (MTRC), School of Allied Health and Social Care, Anglia Ruskin University, Chelmsford, UK; School of Nursing and Midwifery, University of Plymouth, Plymouth, UK
  • Heidi Van Den Bulck Medische Oncologie, AZ Imelda, Bonheiden, Belgium
  • Julie Bastin Medische Oncologie, Heilig Hart ziekenhuis, Lier, Belgium
  • Verbiest Annelies Department of Oncology, Multidisciplinary Oncological Center Antwerp, Antwerp University Hospital, Edegem, Belgium; Center for Oncological Research (CORE), Antwerp University, AntwerpMedische Oncologie, UZAntwerpen, Antwerpen, Belgium
  • Christof Vulsteke Center for Oncological Research (CORE), Antwerp University, Antwerp Medische Oncologie, UZAntwerpen, Antwerpen, Belgium; Medische Oncologie, Maria Middelares ziekenhuis, Gent, Belgium
  • Peter Schatteman Uro Onco Unit, Urology, AZORG, Aalst, Belgium
  • Daisy Luyten Medische Oncologie, Jessa ziekenhuis, Hasselt, Belgium
  • Sandrine Aspeslagh Medische Oncologie, UZBrussel, Brussel, Belgium
  • Nieves Martinez-Chanza Department of Medical Oncology, Institut Jules Bordet - Hôpital Universitaire de Bruxelles, Université Libre de Bruxelles (ULB), Brussels, Belgium
  • Marlies De Bock Medische Oncologie, AZ Delta, Roeselare, Belgium
  • Thomas Meyskens Medische Oncologie, Klina, Brasschaat, Belgium
  • Jolanda Verheezen Medische Oncologie, Trudo Ziekenhuis, St Truiden, Belgium
  • Barbara Brouwers Medische Oncologie, St Jan ziekenhuis, Brugge, Belgium
  • Benoit Beuselinck General Medical Oncology, University Hospital Leuven, Leuven, Belgium

DOI:

https://doi.org/10.2340/1651-226X.2025.43876

Keywords:

Renal cell carcinoma, immune checkpoint inhibitors, optimal treatment duration, treatment discontinuation

Abstract

Background and purpose: Optimal treatment duration is unknown in metastatic renal cell carcinoma (mRCC) responding to immune checkpoint inhibitors (ICPIs). Prolonged treatment can lead to late toxicity, burden for day clinics and financial impact.

Patients and methods: This multicenter retrospective study included mRCC patients responding to ipilimumab/nivolumab in first-line or nivolumab in later lines, who were treated for at least 21 months and did not stop for toxicity. Progression-free survival (PFS), overall survival (OS), and cancer-specific survival (CSS) were modeled non- and semi-parametrically. The effect of elective ICPI discontinuation (i.e. treatment interruption at the clinician’s discretion) between 21 and 25 months on PFS was assessed by a causal inference approach using artificial censoring along with inverse probability of censoring weighting.

Results: Ninety-five patients were included with a median follow-up of 62.1 (95% confidence interval [CI]: 57.3–67.5) months. Fifty-four received ipilimumab/nivolumab, whereas 41 patients received nivolumab, for a median treatment duration of 33.8 (95% CI: 28.5–39.6) months.

Fifty-seven patients discontinued ICPIs electively. Three-year PFS after discontinuation was 57.1% (95% CI: 34.3–95.1), 3-year OS 67.5% (95% CI: 37.0–100.0), and 3-year CSS 90.0% (95% CI: 73.2–100.0).

Fifteen (15.8%) patients discontinued ICPIs between 21 and 25 months. Compared to 80 patients who were treated longer, they had more often a metachronous metastatic pattern (p = 0.048) and a complete response (p = 0.045). Elective ICPI stop between 21 and 25 months did not significantly impact the hazard for progression/death (adjusted HR 1.08, 95% CI: 0.64–1.84, p = 0.766).

Interpretation: Among mRCC patients responding to ICPI, elective therapy discontinuation approximately 24 months after initiation does not appear to compromise outcomes compared to continuing therapy.

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2025-07-30

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Decruyenaere, A., Christine, G., Sylvie, R., Annouschka, L., Seront, E., Everaert, E., … Beuselinck, B. (2025). Optimal treatment duration in metastatic renal cell carcinoma patients responding to immune checkpoint inhibitors: should we treat beyond two years?. Acta Oncologica, 64, 979–988. https://doi.org/10.2340/1651-226X.2025.43876

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Vol. 64 (2025): Acta Oncologica

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Copyright (c) 2025 Alexander Decruyenaere, Gennigens Christine, Rottey Sylvie, Laenen Annouschka, Emmanuel Seront, Els Everaert, Philip R Debruyne, Heidi Van Den Bulck, Julie Bastin, Verbiest Annelies, Christof Vulsteke, Peter Schatteman, Daisy Luyten, Sandrine Aspeslagh, Nieves Martinez-Chanza, Marlies De Bock, Thomas Meyskens, Jolanda Verheezen, Barbara Brouwers, Benoit Beuselinck

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