A real-world experience of immune checkpoint inhibitors (ICI) in metastatic renal cell carcinoma (mRCC).

Abstract

647 Background: ICI therapy has changed the treatment landscape in mRCC. Here we present the safety and efficacy of ICIs used in an academic medical center (UT Southwestern Medical Center) and affiliated county hospital (Parkland Hospital). Methods: All mRCC patients (pts) treated with at least one dose of ICI from 2014 - 2018 were identified. Baseline characteristics were collected at the start of ICI. Outcomes included objective response rate (ORR) as determined by RECISCT v1.1, time to next treatment (TNT) and overall survival (OS). Immune-related adverse events (irAE) were graded according to CTCAE v4.0. Kaplan-Meier methods and Cox proportional hazards regression models were used to estimate survival and generate hazard ratios (HR). Results: We identified 177 pts with mRCC, including 31 at the county hospital, who received at least one dose of ICI. 140 (79.1%) pts were intermediate or poor risk by IMDC, and 149 (84.2%) had clear cell histology. 127 (71.8%) received nivolumab monotherapy, 40 (22.6%) received ipilimumab and nivolumab, and 10 (5.6%) received ICI with a tyrosine kinase inhibitor. ICI was given in the 1st line in 34 (19.2%) pts, 2nd line in 77 (43.5%) pts, and the 3rd or later line in 29 (16.4%) pts. The ORR was 18.6% (33/177), and there were 6 (3.4%) complete responses. The median TNT and OS was 8.9 (95% CI; 7.1-10.6) and 26.7 (95% CI; 22.4-30.9) months, respectively. In multivariate analysis (MVA) of TNT including sex, nephrectomy status, IMDC risk group, histology, and number of organs involved, only number of organs involved (HR: 1.27; 95% CI: 1.12-1.45; p = 0.0003) and non-ccRCC subtype (HR: 2.63; 95% CI: 1.63-4.24; p <0.0001) retained statistical significance. MVA of OS revealed similar findings, with number of involved organs (HR: 1.49; 95% CI: 1.97-7.45; p < 0.0001) and non-ccRCC subtype (HR: 3.83; 95% CI: 1.97-7.45; p <0.0001) correlating with worse survival. irAEs were observed in 77 pts (43.5%) with 42 (23.7%) pts experiencing a grade 3/4 irAE. Conclusions: ICI therapy is safe and efficacious in the real world setting. Clinical and laboratory variables, including the IMDC risk score, do not consistently predict outcomes in this heterogeneous cohort.