Background: Nivolumab was the first immune checkpoint inhibitor to gain FDA approval for use in the treatment of renal cell carcinoma (RCC), however only a quarter of patients respond to nivolumab monotherapy (Nivo). More recently, the combination of ipilimumab and nivolumab (Ipi/Nivo) gained approval as first-line therapy in RCC with better outcomes than previously described with Nivo. Whether Ipi/Nivo can rescue RCC patients who progress on Nivo is an important question that remains unanswered. We sought to evaluate the oncologic benefit of treating metastatic RCC patients with Ipi/Nivo following progression on Nivo at our institution.

Methods: A systematic medical record search was conducted to identify patients with RCC who had been treated with Ipi/Nivo following progression on Nivo from 2013 to Jan 31, 2018. Clinical benefit after starting Ipi/Nivo was measured by time to next therapy (TNT), overall survival (OS), and objective responses defined by RECIST v1.1. Kaplan Meier methods were used to analyze event-free survival.

Results: 90 RCC patients were treated with Nivo from 2013 until Jan 31st, 2018. 17 (19%) of these patients received Ipilimumab following progression. Baseline characteristics of this subgroup were similar to the entire cohort. 13 (76.5%) had intermediate or poor risk disease by the Heng prognostic risk score. 6 (35.3%) patients had one prior line of therapy and 11 (64.7%) had two or more prior lines of therapy. The median duration of nivolumab monotherapy was 11.9 (95% CI; 4.4 - 13.0) months. Following the addition of ipilimumab at progression, the median TNT was 3.9 (95% CI; 3.3 to 7.0) months and the median OS was 20.3 (95% CI; 12.1 - 22.1) months. There were no objective responses to Ipi/Nivo following Nivo alone. Stable disease was the best overall response in 5 (29%) patients, and the remainder demonstrated progressive disease. One patient had stable disease lasting 11 months. Immune related adverse events were observed in 8 (47%) of patients resulting in cessation of therapy for 1 patient.

Discussion: In this analysis, Ipi/Nivo did not confer substantial treatment benefit to patients who had already progressed on Nivo alone. The were no objective responses, and most patients were started on the next line of therapy at their first set of imaging studies. These patients still demonstrated approximately a 2-year OS suggesting that alternative agents, such as TKIs, remain effective treatments in this population. Prospective evaluation is warranted to further evaluate the utility of Ipi/Nivo following progression on Nivo alone.

Citation Format: Roy M. Elias, Nirmish Singla, Isaac A. Bowman, Payal Kapur, Raquibul Hannan, Hans Hammers, James Brugarolas. Outcomes of combined ipilimumab and nivolumab therapy following progression on nivolumab monotherapy in renal cell carcinoma: A retrospective cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4106.