Real-world efficacy and toxicity of ipilimumab and nivolumab as first line treatment of metastatic renal cell carcinoma (mRCC) in a subpopulation of elderly and poor performance status patients.

367 Background: Ipilimumab and nivolumab (ipi/nivo) improved overall survival (OS) and response rates compared to sunitinib in the pivotal Checkmate 214 trial of intermediate/poor risk mRCC. A subgroup analysis showed no significant difference in OS for ipi/nivo in pts 65 to 75 years old (yo), as well as pts >75 yo. In another subgroup analysis, Karnofsky performance status (KPS) <70 was associated with worse median OS compared with pts with KPS ≥ 70. We evaluated efficacy and toxicity of ipi/nivo in an older and frailer population in a real-world cohort. Methods: Analysis was conducted on a real-world cohort with mRCC (N=378) treated with ipi/nivo as first line treatment from the Canadian Kidney Cancer Information System (CKCis) database from January 2011 to March 2022. Median follow-up was 14.3 m (range 0 to 87.6). A comparison was made between outcomes and toxicity in pts ≥ versus (vs) <70 yo, ≥ vs <75 yo, KPS < vs ≥70, and ≥70 yo with KPS <70 vs <70 yo with KPS >70. Toxicity was graded as per CTCAE v4.03 or any toxicity that resulted in a dose/schedule change. OS, progression free survival (PFS) and time to treatment failure (TTF) were calculated by Kaplan-Meier analysis. Log rank tests were used for comparison between groups. Multivariate analysis was done including IMDC for all outcomes. Results: Median OS was worse in older patients at 30.0 m in pts ≥ 70 yo vs 45.4 m in pts < 70 yo (p=0.060), and 19.0 m in the pts ≥ 75 yo vs 45.5 m in pts < 75 yo (p=0.003) despite similar disease control rates and toxicity. Median PFS was similar in younger and older pts: < vs ≥ 70 yo (p=0.560) and < vs ≥ 75 yo (p=0.296). Median TTF was comparable in < 70 yo and ≥ 70 yo (p=0.106) and < 75 and ≥ 75 yo groups (p-value=0.733). Median OS, PFS and TTF were comparable in pts KPS < 70 vs pts KPS ≥ 70 and in pts ≥70 yo with KPS < 70 vs pts < 70 yo with KPS >70. Adjusted and unadjusted analysis showed no difference in OS and PFS between groups. Conclusions: Use of ipi/nivo in mRCC in older patients was associated with inferior OS, while decreased performance status had equivalent OS. Both groups had equivalent TTF and PD without higher toxicity. We believe that ipi/nivo is a reasonable treatment option for older and low performance status patients. [Table: see text]