Outcomes of patients with metastatic clear-cell renal cell carcinoma treated with second-line VEGFR-TKI after first-line immune checkpoint inhibitors

Abstract

Immune checkpoint inhibitors (ICI) are being increasingly utilized in the front-line (1L) setting of metastatic clear-cell renal cell carcinoma (mccRCC). Limited data exist on responses and survival on second-line (2L) VEGFR-TKI therapy after 1L ICI therapy. This is a retrospective study of mccRCC patients treated with 2L VEGFR-TKI after progressive disease (PD) with 1L ICI. Patients were treated at MD Anderson Cancer Center or Memorial Sloan Kettering Cancer Center between December 2015 and February 2018. Objective response was assessed by blinded radiologists’ review using RECIST v1.1. Descriptive statistics and Kaplan-Meier method were utilized. Seventy patients were included in the analysis. Median age at mccRCC diagnosis was 59 years; 8 patients (11%) had IMDC favorable-risk, 48 (69%) had intermediate-risk, and 14 (20%) had poor-risk disease. As 1L therapy, 12 patients (17%) received anti-PD-(L)1 monotherapy with nivolumab or atezolizumab, 33 (47%) received nivolumab plus ipilimumab, and 25 (36%) received combination anti-PD-(L)1 plus bevacizumab. 2L TKI therapies included pazopanib, sunitinib, axitinib, and cabozantinib. On 2L TKI therapy, one patient (1.5%) achieved a complete remission (CR), 27 patients (39.7%) a partial response (PR), and 36 patients (52.9%) stable disease (SD). Median progression-free survival (mPFS) was 13.2 months (95% CI: 10.1, NA). Forty-five percent of subjects required a dose reduction, and twenty-seven percent of patients discontinued treatment due to toxicity. In this retrospective study of patients with mccRCC receiving 2L TKI monotherapy following 1L ICI, we observed 2L antitumor activity and tolerance comparable to historical data for 1L TKI.