Clinical outcomes and tolerability of ipilimumab/nivolumab in older (≥70 years) versus younger patients with metastatic clear cell RCC: A multi-institutional analysis of 514 patients.

Abstract

444 Background: Ipilimumab plus nivolumab (I/N) is a standard first-line treatment for metastatic clear cell renal cell carcinoma (mccRCC), yet data in elderly patients remains less well characterized. Age-related immune changes, comorbidities, and polypharmacy may affect treatment tolerance and efficacy, yet data on discontinuation rates and outcomes by age are limited. We evaluated treatment tolerance, and outcomes of patients aged ≥70 versus < 70 years receiving first-line I/N for mccRCC. Methods: We conducted a retrospective study of patients with mccRCC treated with first-line I/N at Memorial Sloan Kettering Cancer Center and MD Anderson Cancer Center. Clinical data were extracted from electronic health records. Patients were stratified by age at treatment initiation (< 70 vs ≥70 years). Kaplan-Meier methods estimated time on treatment (first I/N dose to last dose of I/N or single-agent nivolumab), time to second-line therapy (TT2), and overall survival (OS); comparisons were made via log-rank tests. Rates of induction completion and discontinuation for adverse events (AEs) were compared using Fisher’s exact test. Results: Among 514 patients (median age 62 years; range 33–85); 98 (19%) were ≥70 years and 9 (1.7%) were ≥80 years. Baseline characteristics including gender, stage, IMDC risk, and metastatic sites were similar, though sarcomatoid/rhabdoid features were less frequent in older patients (20% vs 39%). Fewer older patients completed all four induction doses (53% vs 65%; p= 0.04), but median time on I/N regimen was comparable across the two cohorts (see table). AE-related discontinuation occurred more often in older adults (42% vs 25%, p < 0.001). Median TT2 was 27 months (95% CI, 13-NE) in older patients and 13 months (95% CI, 11-16) in younger patients (p=0.005). Median OS did not differ between groups with 5.0 months (95% CI 2.9-7.4) and 4.2 months (95% CI, 3.5-5.8), respectively (p= 0.85). Conclusions: Patients with mccRCC aged ≥70 vs. < 70 years achieved comparable time on treatment and OS with first-line I/N, despite lower rate of induction completion in the older group. These findings support the use of I/N in appropriately selected older adults, highlighting the importance of individualized treatment decisions. <70 years (n=416) ≥70 years (n=98) p-value Sarcomatoid or rhabdoid features, n (%)  160 (39%) 20 (20%) <0.001 Completion of four I/N doses, n (%)  268 (65%) 52 (53%) 0.04 AE-related discontinuation, n (%)  101 (25%) 41 (42%) <0.001 Median time on therapy, mo (95% CI)  5.3 (4.4, 6.1) 4.2 (2.8–8.0) 0.83 Median TT2, mo (95% CI)  13 (11–16) 27 (13–NE) 0.005 Median OS, years (95% CI)  4.2 (3.5–5.8) 5.0 (2.9–7.4) 0.85