ORCID
- Philip R Debruyne: 0000-0001-5438-9697
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.
DOI Link
Publication Date
2025-07-30
Publication Title
Acta Oncologica
Volume
64
ISSN
0284-186X
Acceptance Date
2025-01-01
Deposit Date
2025-11-03
Funding
PRD reports advisory board roles with Astellas Pharma, Ipsen, MSD and travel support from Ipsen; He hold stocks in Mural Oncology PLC UCB and Biocartis Group NV. CV reports advisory board roles with Astellas Pharma, Astrazeneca, Bayer, BMS, GSK, Janssens-Cilag, Leo Pharma, Merck, MSD, Pfizer. He reports a non-financial interest research grant with MSD. ES reports consultancy fees for BMS, Ipsen and MSD. CG reports grants for Astrazeneca, GSK, Deciphera; She has performed consultancy for Ipsen, GSK, MSD and received honoraria for MSD, BMS, Ipsen, Pfizer, Pharmamar, Astrazeneca, GSK as well as travel support from Ipsen, Pharmamar, Pfizer, MSD, GSK, Astrazeneca; She reports advisory board roles with MSD, BMS, Ipsen, Astrazeneca, GSK, Genmab, Pharmaand GmbH and Eisai. MCN reports grants The authors are grateful to the patients who were included in the study and to all the persons who helped in data collection. There was no specific funding for this project. BB holds an FWO Vlaanderen senior clinical research mandate.
Keywords
Humans, Carcinoma, Renal Cell/drug therapy, Immune Checkpoint Inhibitors/administration & dosage, Kidney Neoplasms/drug therapy, Male, Retrospective Studies, Female, Aged, Middle Aged, Nivolumab/administration & dosage, Ipilimumab/administration & dosage, Progression-Free Survival, Aged, 80 and over, Adult, Time Factors, Duration of Therapy, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Follow-Up Studies, treatment discontinuation, immune checkpoint inhibitors, optimal treatment duration, Renal cell carcinoma
First Page
979
Last Page
988
Recommended Citation
Decruyenaere, A., Christine, G., Sylvie, R., Annouschka, L., Seront, E., Everaert, E., Debruyne, P., Van Den Bulck, H., Bastin, J., Annelies, V., Vulsteke, C., Schatteman, P., Luyten, D., Aspeslagh, S., Martinez-Chanza, N., De Bock, M., Meyskens, T., Verheezen, J., Brouwers, B., & 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, pp. 979-988. Available at: 10.2340/1651-226X.2025.43876
