Checkpoint Inhibitors in the Management of Renal Cell Carcinoma with Sarcomatoid Features

Metastatic renal cell carcinoma (RCC) with sarcomatoid features carries a poor prognosis and does not respond well to therapy with VEGF inhibitors. Based on results of CheckMate 025 trial, Nivolumab, a programmed cell death-1 (PD-1) inhibitor, was approved for treatment of metastatic RCC in November 2015. However, the efficacy of checkpoint inhibitors in metastatic RCC with sarcomatoid features is unknown.

We conducted a retrospective chart review of all patients who were diagnosed with metastatic RCC containing sarcomatoid component at Roswell Park Cancer Institute between Jan 2010 to March 2017. Patient characteristics, previous therapies, treatment duration, drug-related adverse events and outcomes including response and overall survival were analyzed.

We identified 34 patients with metastatic RCC who had sarcomatoid component on kidney biopsy. Baseline characteristics of all patients are summarized in Table 1. Ten patients received Checkpoint Inhibitors (CPI) after failure of first-line therapy while 24 patients were treated without the use of CPI. Median age in CPI group was 61.5 (Range: 42-86) years and 58 (Range: 23-80) years in the non-CPI group. Most common reason for discontinuation of CPI was disease progression. One patient developed grade IV toxicity with colitis, nephritis and pneumonitis that was successfully treated with steroids.

After a median follow up of 10 months, 5 out of 10 patients (50%) in the CPI group and 5 out of 24 patients (20.8%) in control group are alive. The median survival from the time of diagnosis of metastatic disease was significantly higher in patients who received immunotherapy (54 vs. 6 months, P<0.001).

Our data indicates that use of checkpoint inhibitors for the treatment of metastatic RCC with sarcomatoid features is associated with improved survival and is relatively well tolerated.