[en] [en] 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.
Disciplines :
Oncology
Author, co-author :
Decruyenaere, Alexander; Department of Medical Oncology, Ghent University Hospital, Gent, Belgium
Gennigens, Christine ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'oncologie médicale
Sylvie, Rottey; Department of Medical Oncology, Ghent University Hospital, Gent, Belgium
Annouschka, Laenen; Biostatistics and Statistical Bioinformatics Center, Leuven, Belgium
Everaert, Els; Medische Oncologie, VITAZ, St Niklaas, Belgium
Debruyne, Philip R; 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
Van Den Bulck, Heidi; Medische Oncologie, AZ Imelda, Bonheiden, Belgium
Annelies, Verbiest; Department of Oncology, Multidisciplinary Oncological Center Antwerp, Antwerp University Hospital, Edegem, Belgium, Center for Oncological Research (CORE), Antwerp University, AntwerpMedische Oncologie, UZAntwerpen, Antwerpen, Belgium
Vulsteke, Christof; Center for Oncological Research (CORE), Antwerp University, Antwerp Medische Oncologie, UZAntwerpen, Antwerpen, Belgium, Medische Oncologie, Maria Middelares ziekenhuis, Gent, Belgium
Schatteman, Peter; Uro Onco Unit, Urology, AZORG, Aalst, Belgium
Martinez-Chanza, Nieves; Department of Medical Oncology, Institut Jules Bordet - Hôpital Universitaire de Bruxelles, Université Libre de Bruxelles (ULB), Brussels, Belgium
De Bock, Marlies; Medische Oncologie, AZ Delta, Roeselare, Belgium
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.
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