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

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.