Severe immune-related Adverse Events (irAEs) develop in 10-27% of patients treated with Immune-Oncology (IO) [Powles (Lancet 391:748-757, 2018); Galsky (Lancet 395:1547-1557, 2020); Haanen (Ann Oncol 28:119-142, 2017)].
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 irAEs.
We 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).
18/204 (8.8%) patients had early treatment interruption for serious (G3-G4) irAEs. Early was defined as interruption of IO after only 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 the study group, 12/18 (66.6%) were free from progression at 6 months since 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).
ICIs seem to maintain efficacy even after early interruption due to severe irAE.
Journal of translational medicine. 2021 Aug 03*** epublish ***
Marco Stellato, Giuseppe Procopio, Ugo De Giorgi, Marco Maruzzo, Davide Bimbatti, Alessia Mennitto, Andrea Sbrana, Giandomenico Roviello, Chiara Casadei, Pierangela Sepe, Sandro Pignata, Daniele Santini
Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. ., Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori, Meldola, Italy., Medical Oncology Unit 1, Department of Oncology, Istituto Oncologico Veneto IOV IRCCS, Padua, Italy., Division of Oncology, University Hospital "Maggiore Della Carità ", Novara, Italy., Department of Surgical, Medical and Molecular Pathology and Critical Area Medicine, University of Pisa, Pisa, Italy., Department of Health Sciences, University of Florence, Florence, Italy., Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione "G. Pascale", Naples, Italy., Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/34344414
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