Efficacy of Immunotherapy in Advanced Renal Cell Carcinoma (RCC) Patients Despite the Early Treatment Interruption Due to Serious Immune-related Adverse Events. Meet-Uro 13 Trial on Behalf of the MeetUro Investigators
BackgroundSevere immune-related Adverse Events (irAEs) develop in 10-27% of patients treated with anti-Cytotoxic T-Lymphocyte Antigen (CTLA)-4, in amount 12-20% of patients treated with anti-programmed cell death (PD)-1 and 15-20% of patients treated with anti-programmed death-ligand (PD-L)-1(1–3). The aim of our study was to evaluate efficacy and clinical outcome of metastatic renal cell carcinoma (mRCC) patients who stopped Immune Checkpoint Inhibitors (ICIs) due to early Grade (G) 3-G4
... rade (G) 3-G4 irAEs.MethodsWe retrospectively collected data from 204 mRCC patients treated with ICIs in 6 Italian referral centers adhering to the Meet-Uro group, between February 2017 and January 2020. To properly weight the results, patients who did not report early G3-G4 toxicities have been included as control group.Primary endpoint was to evaluate 6 months Progression Free Survival (PFS) after early treatment interruption for Grade (G) 3-4 toxicities compared to the control group. Secondary endpoints were to evaluate Time to treatment failure (TTF) and overall survival (OS) in both groups. All statistical analyses were performed using SPSS software (version 19.00, SPSS, Chicago).Results18/204 (8.8%) patients had early treatment interruption for serious (G3-G4) irAEs. Early was defined as interruption of IO after one or two administrations. Immune related nephritis and pancreatitis were the most common irAE that lead to treatment interruption. 6/18 patients received IO-IO combination whereas 12/18 patients antiPD1. In patients who interrupted treatment due to irAE, 12/18 (66.6%) were free from progression at 6 months from IO interruption, TTF was 1.6 months (95%CI 1.6-2.1), mPFS was 7.4 months (95%CI 3.16-11.6) and mOS was 15.5 months (5.1-25.8). In the control group 111/184 (60.3%) patients were free from progression at 6 months, TTF was 4.6 months (95%CI 3.5-5.6), mPFS was 4.6 months (95%CI 3.5-5.6) and mOS was 19.6 months (95%CI 15.1-24.0). In the overall population, mPFS was 5.0 months (95%CI 4.0-5.9) and mOS was 19.6 months (95%CI 15.1-24.0). ConclusionsICIs seem to maintain efficacy even after early interruption due to severe irAE.