Safety and efficacy of retreatment with immune checkpoint inhibitors (ICIs) in patients with metastatic RCC (mRCC) who have previously received an ICI.

Abstract

698 Background: Several ICIs are approved for use in first and subsequent lines of therapy in mRCC, either alone or in combination with another ICI or targeted therapy. There is limited data on whether patients who receive an ICI derive benefit from a subsequent line of ICI-based therapy. Methods: We reviewed mRCC patients at our institution who were treated with an ICI between 2009 and 2018 having previously received ICI-based therapy. The primary outcomes of interest were radiologic response and time to treatment failure (TTF) on ICI retreatment. Immune-related adverse events (irAEs) were graded using CTCAE v5.0. Results: A total of 31 patients were retreated with an ICI, either alone (n=15) or in combination with another ICI (n=8), tyrosine kinase inhibitor (n=2) or investigational agent (n=6); reasons for discontinuation of prior ICI were disease progression (n=23), toxicity (n=7) and study completion (n=1). Median age at the start of first-line therapy was 62 years and the majority of patients (n=30, 90%) had International Metastatic RCC Database Consortium intermediate- or poor-risk disease; median follow-up was 3.4 years (95% CI 2.5-4.6). The median number of lines of therapy received prior to ICI retreatment was 3 (range 1-7). Of 27 evaluable patients, 3 (11%) had a partial response (PR) to ICI retreatment (2 with ICI-ICI combination therapy and 1 with single-agent ICI), 13 (48%) had stable disease, and 11 (41%) had progressive disease (PD) as their best response; of the 3 with a PR, 2 had a PR and 1 had SD to prior ICI therapy. In comparison, 13 of 31 patients (42%) had a PR or better to first ICI-based therapy, with 4 (13%) having PD. Median TTF on ICI retreatment was 3.2 months (95% CI 1.8-5.2), compared to 8.2 months (3.3-10.0) on prior ICI. 19 patients experienced an irAE with ICI retreatment, with 8 (26%) suffering a grade 3 or higher irAE. Conclusions: Retreatment with ICIs after prior therapy with an ICI was relatively safe but demonstrated limited efficacy. Additional data, ideally from prospective studies, assessing outcomes of retreating patients with ICIs are needed to determine whether using different ICIs in sequence has a role in treatment of mRCC.