ASCO GU 2021: Safety and Efficacy of Nivolumab in Older Patients with Renal Cell Carcinoma: Results of a Sub-Group Analysis of the GETUG-AFU 26 NIVOREN Multicenter Phase II Study

(UroToday.com) The NIVOREN GETUG AFU 26 study is a French multicenter prospective study to evaluate the safety and efficacy of nivolumab in a broad “real world setting” in metastatic renal cell carcinoma (mRCC) after failure of 1 or 2 tyrosine kinase inhibitors. Initial results for this trial were presented at the 2019 GU ASCO annual meeting. Regarding the safety data, 129 patients (17.9%) had at least one grade ≥ 3 treatment-related adverse event, including asthenia (3.5%), metabolic disorders (2.1%), gastrointestinal disorders (2 .2%), musculoskeletal (1.7%), renal disorders (1.4%), hematologic (1.3%). There six treatment-related mortalities. Median progression-free survival was 3.2 months (95%CI 2.9-4.6) and the 12-month OS rate was 69% (95%CI 66-73). At the 2021 GU ASCO annual meeting, Dr. Loic Mourey and colleagues presented results of a subgroup analysis specifically assessing safety and efficacy in older patients.


NIVOREN GETUG AFU 26 enrolled 720 patients between February 2016 and July 2017 across 27 institutions in France. Inclusion criteria allowed performance status 0-2, >2 prior lines of therapy, prior mTOR inhibitor therapy, asymptomatic brain metastases, and impaired renal function (CrCl >40 mml/min). Patients must have had a component of clear cell histology.  The primary objective of the trial was safety assessed by grade ≥ 3 treatment-related adverse events. For this analysis, results of older patients more than 70 years of age (n=205, 28.5%) were compared with their younger counterparts.

Among the 205 patients that were ≥ 70 years of age, there were 107 (14.9%) patients 70-75 years of age, 68 (9.4%) patients 75-80 years of age, and 30 (4.2%) patients >80 years of age; these patients were compared to 515 patients <70 years of age. Patient characteristics were similar in younger and older patients except for:

  • Fewer IMDC poor prognostic patients ≥ 75 years of age
  • Fewer nephrectomy patients ≥ 80 years of age
  • Fewer brain metastasis in patients ≥ 70 years of age
  • More impaired renal function in older patients
Elderly patients were heavily pretreated, comparable to their younger counterparts, including ~25% of patients receiving >2 prior lines of therapy, ~1/3 of patients ≥ 80 years of age receiving everolimus before trial enrollment. Treatment duration was similar across age groups despite a rate of discontinuation for treatment-related adverse events increasing with age. Reasons for treatment discontinuation for older patients (versus younger patients) was more likely to be due to adverse events or physician/patient decision than secondary to disease progression. Regarding efficacy, there was a non-significant trend toward improved response rate and progression-free survival and lower overall survival with increasing age:

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Dr. Mourey concluded this presentation of elderly patients in the GETUG-AFU 26 NIVOREN with the following take-home messages:

  • In this large “real world” setting study of nivolumab in mRCC after failure of at least one TKI, a significant number of old patients were included
  • NIVOREN provides us with valuable information regarding the prescription of nivolumab in older patients with mRCC, even if we lack geriatric data to precisely describe this population
  • Compared to their younger counterparts, older patients in NIVOREN had the same treatment duration, have more treatment-related adverse events, stop treatment more frequently for adverse events or physician/patient decision, and tend to experience better activity of nivolumab
  • Age alone should not prevent us from prescribing nivolumab in older patients with mRCC, however careful assessment before prescription and close follow-up during treatment of older patients is mandatory

Presented by: Loic Mourey, MD, Institut Claudius Regaud/IUCT-Oncopole, Toulouse, France

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md during the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (#GU21), February 11th-February 13th, 2021
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