Outcomes with first-line ipilimumab and nivolumab for patients with metastatic renal cell carcinoma by number of doses.

540 Background: Ipilimumab (IPI) and nivolumab (NIVO) are standard first-line systemic therapy for patients with metastatic renal cell carcinoma (RCC). The regimen is administered in combination once every 3 weeks for 4 doses, followed by NIVO maintenance. The dose and frequency of IPI appears to correlate with treatment safety and tolerability across cancer types. Further, studies in advanced melanoma have demonstrated that the efficacy of IPI + NIVO is largely driven by the first two doses in many patients (Postow MA et al., J Clin. Oncol. 2022). We assessed outcomes with IPI + NIVO by number of doses given in patients with metastatic RCC. Methods: We conducted a retrospective study of patients with metastatic RCC at Memorial Sloan Kettering Cancer Center treated with first-line IPI + NIVO. Baseline characteristics and treatment outcomes were obtained from electronic health record review. We calculated overall survival (OS) by the Kaplan-Meier method starting at 12 weeks after initiation of combination therapy, including all patients who were still alive and being followed at that time point and excluding those who had disease progression prior to completing 4 doses. We compared survival rates at 12 and 18 months and median OS for patients who received 4 doses versus those who received fewer than 4 doses. Results: Patients with metastatic RCC treated with first-line IPI + NIVO were included (N=222); 77% were male, 85% had clear cell RCC, 48% had sarcomatoid and/or rhabdoid features, and 87% had IMDC intermediate or poor risk disease. Regarding IPI + NIVO, 145 patients (65%) received all 4 doses, 30 (14%) received 3 doses, 21 (9%) received 2 doses, and 26 (12%) received 1 dose. The most common reasons for not completing all 4 doses (77, 35%) were toxicity (57%) and disease progression (21%). All 145 patients who received 4 doses and 44 who received fewer than 4 doses for reasons other than early progression or death were included in the analysis. OS in the 4 dose and <4 dose group at 18 months was 83% (95% CI: 76%, 89%) and 79% (95% CI: 63%, 88%), respectively. Conclusions: In this observational analysis, we found comparable OS rates in those patients who received all 4 doses of IPI + NIVO compared to those who received fewer than 4 doses for reasons other than disease progression, primarily toxicity. Four Doses of IPI + NIVO (N=145) Fewer Than Four Doses of IPI + NIVO, Excluding Early Disease Progression (N=44) 12-month OS (95% CI) 89% (82%, 93%) 86% (72%, 94%) 18-month OS (95% CI) 83% (76%, 89%) 79% (63%, 88%) Median OS, months (95% CI) 67.1 (40.1, NR) 82.5 (27.1, 109.3) Log-rank p value = 0.595