ASCO GU 2022: The Impact of Baseline Peripheral Cytokines on Survival in Metastatic Clear Cell Renal Cell Carcinoma Treated With Nivolumab: NIVOREN GETUG-AFU 26 Translational Study

( In session on the third day of the American Society for Clinical Oncology (ASCO) Genitourinary Cancer Symposium 2022, Poster Session C focused on Renal Cell Cancer; Adrenal, Penile, Urethral, and Testicular Cancers. In this session, Dr. Carril presented results of a translational research program embedded with the NIVOREN GETUG-AFU 26 study which reported the real world safety and efficacy of nivolumab in patients with renal cell carcinoma (RCC). One of the main focuses of this translational research program was to quantify baseline cytokine levels and correlate them with outcomes to nivolumab.

To do so, the authors first assembled a training cohort (n=80) comprised of extreme responder patients treated with nivolumab as part of the phase II NIVOREN GETUG-AFU 26 trial. A panel of 14 different plasma cytokines and proteins (VEGF, VCAM-1, IL-6, IL-7, IL-8, IL-10, APRIL, BAFF, 4-1BB, BCA, SDF-1, MDC, IFN-gamma and TNF-alpha) were quantified for each plasma sample using the Elisa-based Meso Scale Discovery electrochemiluminescence assay. The authors then tested the association between baseline cytokine levels and objective response rate (ORR), progression-free survival (PFS) and overall survival (OS).

The initial cytokine analysis including 80 patients of whom 40 were deemed responders to nivolumab and 40 were progressors. The baseline characteristics of this training subset were similar to the overall trial population, with a breakdown in IMDC risk score of 11.3% good-risk disease, 56.3% intermediate, and 32.5% poor.

Over a median follow-up of 21.2 months, overall survival data was immature with an overall survival rate of 67.3% at 12 months. The median PFS was 3.8 months. Among the 14 different plasma cytokines and proteins tested, 5 demonstrated significant associations with overall survival: increased levels of IL-6 (HR=2.44, p=0.0112), IL-7 (HR=2.38, p=0.0123), IL-8 (HR=2.80, p=0.0045), and VEGF (HR=2.43, p=0.0133) were significantly negatively associated with survival while increased levels of 4-1BB was associated with improved OS (HR=0.39, p=0.0375).

ASCO GU 2022_Carril_0 

Higher levels of IL-8 (HR=2.50, p=0.0133) and VEGF (HR=1.96, p=0.0132) were associated with worse PFS and worse ORR (IL-8: p=0.013, and VEGF: p=0.044) though none of the other 14 markers tested showed an association with response.

Thus, the authors conclude that higher baseline plasma levels of IL-6, IL-7, IL-8 and VEGF were significantly associated with worse survival outcomes in mRCC patients treated with nivolumab within the TRAINING cohort of the NIVOREN trial. In contrast, 4-1BB was significantly associated with improved OS. Ongoing works seeks to validate these findings in the overall NIVOREN cohort.

Presented by: Lucia Carril, MD, Institut Gustave Roussy, Villejuif, France

Written by: Christopher J.D. Wallis, University of Toronto Twitter: @WallisCJD during the 2022 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, Thursday Feb 17 – Saturday Feb 19, 2022

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