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

Abstract

Background: Immune checkpoint inhibitors (ICIs) are being increasingly utilised 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) vascular endothelial growth factor-receptor tyrosine kinase inhibitor (VEGFR-TKI) therapy after 1L ICI therapy.

Patients and methods: 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 Response Evaluation Criteria in Solid Tumours v1.1. Descriptive statistics and Kaplan-Meier method were used.

Results: Seventy patients were included in the analysis. Median age at mccRCC diagnosis was 59 years; 8 patients (11%) had international metastatic database consortium favourable-risk disease, 48 (69%) had intermediate-risk disease and 14 (20%) had poor-risk disease. As 1L therapy, 12 patients (17%) received anti-programmed death ligand-1 (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 response, 27 patients (39.7%) a partial response and 36 patients (52.9%) stable disease. Median progression-free survival (mPFS) was 13.2 months (95% confidence interval: 10.1, NA). Forty-five percent of subjects required a dose reduction, and twenty-seven percent of patients discontinued treatment because of toxicity.

Conclusions: In this retrospective study of patients with mccRCC receiving 2L TKI monotherapy after 1L ICI, we observed 2L antitumour activity and tolerance comparable to historical data for 1L TKI.

Keywords: Clear cell renal cell carcinoma; Immune checkpoint inhibitor; Immunotherapy; Immunotherapy refractory; Metastatic kidney cancer; RCC; Renal cell carcinoma; Therapy sequence; VEGFR-TKI; ccRCC.

Copyright © 2019 Elsevier Ltd. All rights reserved.

Figures

Figure 1:

Waterfall Plot of Best Overall Response 68 patients with evaluable disease included, with overall best responses broken down by choice of 2L TKI. 1 patient achieved CR, 27 with PR, 36 with SD, 4 with PD. TKI: tyrosine kinase inhibitor

Figure 2:

Progression-Free Survival (PFS) Median progression free survival by Kaplan-Meier method was 13.2 months (95% CI 10.1 – NA).

Figure 3:

Overall Survival (OS) Median overall survival by Kaplan-Meier was not reached. The 1 year survival probability was 79.6% (95% CI 70.2% – 90.3%).

Figure 4:

Duration of 2L TKI Therapy All 70 patients were included in this swimmer’s plot for duration of therapy, broken down by choice of 2L TKI. TKI end denotes that 2L TKI was discontinued either for progressive disease or for toxicity.