ASCO GU 2022: Association of Adrenal Metastases With Outcomes in Patients With Metastatic Clear Cell Renal Cell Carcinoma Treated With Nivolumab in the GETUG-AFU-26 NIVOREN Phase II Trial

( The Poster Session C on the third day of the American Society for Clinical Oncology (ASCO) Genitourinary Cancer Symposium 2022 focused on Renal Cell Cancer; Adrenal, Penile, Urethral, and Testicular Cancers. In this session, Dr. Billon presented an analysis of the effect of glandular metastasis in patients with metastatic clear cell renal cell carcinoma (mccRCC) treated with nivolumab in the GETUG-AFU-26 NIVOREN phase II trial.

The authors note that glandular metastases including those involving the adrenal, pancreas, thyroid, ovary, breast, or prostate are rare in mccRCC. In prior studies of patients treated with anti-angiogenic therapy, patients with glandular metastases had significantly longer overall survival (OS). However, outcomes for patients with glandular metastases treated with nivolumab are unknown.

To do so, the authors assessed patients treated within the GETUG-AFU 26 NIVOREN trial, a phase II study assessing the activity and safety of nivolumab in patients with mccRCC who failed antiangiogenic therapies (NCT03013335). In this analysis, the authors stratified patients into two subgroups according to the presence of at least one glandular metastasis. Specific analyzes were performed for pancreatic and adrenal metastases. While the primary endpoint was OS, secondary endpoint were progression free survival (PFS) and overall response rate (ORR).

Between February 2016 and July 2017, the NIVOREN trial accrued 720 patients who were treated with nivolumab. Among these 720 patients, 217 patients had glandular metastasis of whom 151 had adrenal and 86 had pancreatic metastases. Clinical characteristics were comparable between the two subgroups except patients with glandular metastases less commonly had IMDC poor risk disease (19% vs 28%) and Furhman grade IV disease (13.5% vs 23.4%). Median time between the diagnosis of metastatic disease and initiation of nivolumab was 3.2 years vs 2 years for patients with and without glandular metastases, respectively, and 2.8 vs 2.1 years for patients with or without adrenal metastasis, respectively.

There was no statistical difference in outcomes between patients with or without glandular metastases.


However, patients with adrenal metastases had worse OS (12-months survival: 64% vs 71.1%; HR 1.51 (1.19-1.92)), shorter PFS (6-months survival: 27.2% vs 36.6%; HR 1.29 (1.07-1.57)) and lower ORR (12.5% [7.6%; 19.0%] vs 23.2% [19.8%; 27.0%]; p = 0.005) compared to patients without adrenal metastases. In multivariable analyses, the presence of adrenal metastases remained a significant predictor for progression-free survival (HR 1.39, 95% CI 1.14-1.69) and overall survival (HR 1.65, 95% CI 1.29-2.10).


In contrast, patients with pancreatic metastases had significantly longer overall survival (12-months survival: 82.3% vs 67.9%; HR 0.59 (0.40-0.85)) in univariate analysis compared to non-pancreatic metastases. However, this did not remain significant on multivariable analyses (HR 0.74, 95% ci 0.50-1.08).


The authors, therefore, conclude that adrenal metastasis is an independent poor prognostic factor for response and survival in the GETUG-AFU 26 NIVOREN phase II trial and limited activity of nivolumab is observed in this patient subset.

Presented by: Emilien Billon, MD, Institut Paoli-Calmettes, Marseille, 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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