18th Meeting of the EAU Section of Oncological Urology (ESOU21)

ESOU 2021: Does Every Metastatic Patient Need Immunotherapy in a First-Line Setting?

(UroToday.com) The third Renal Cancer session at this year’s European Association of Urology (EAU) Section of Oncological Urology (ESOU) 2021 virtual meeting focused on the management of patients with advanced and metastatic disease. In this session, Dr. Ravaud addressed the question, “Does every metastatic patient need immunotherapy in a first-line setting?”

Dr. Ravaud began by answering this question in the affirmation though, in the future, this may change. He emphasized that IO+IO or IO+TKI have, in phase III trials, demonstrated significant benefits in nearly every meaningful endpoint compared to TKI alone. However, he emphasized that there are a number of subgroups for whom the data are somewhat less clear.

For example, the benefit of combined, IO-based treatment approaches appears to be much smaller, it at all present, for older patients based on subgroup analyses of the phase III trials. In the data presented below, assessing overall survival, there is a significantly diminished benefit for older patients. Thus, he advocated for “real world” data to drive evidence-based decisions for these patients.


The second subgroup that Dr. Ravaud highlighted was those patients with a severe or symptomatic auto-immune disease, such as inflammatory bowel disease, in which the risk-benefit balance may be significantly tipped given their risk of toxicity.

Further, among patients with good risk disease, Dr. Ravaud considered the data less clear. While pembrolizumab + axitinib demonstrated benefit in objective response rate and complete response rate in this group, other combination therapies have not proven such benefit. Further, no study has demonstrated differences in overall survival for the IO-based approaches in this group. Thus, in terms of long-term outcomes, he considered this a pending question regarding sequenced therapy.

Moving forward, he suggested that molecular biologically driven treatment selection, based on parameters for angiogenesis and immune infiltration to guide treatment decisions. He highlighted preliminary data demonstrating a predictive benefit to TKI based therapy for patients with an Angio-high signature. He then presented data from the BIONIKK trial which, using transcriptomic analysis, subgroups of clear cell renal cell carcinoma (ccRCC) could be distinguished in which TKI based treatment approaches were preferable. Further immune signatures also demonstrate the “inefficiency” of immunotherapy-based approaches and thus may allow for sparing of these.

In conclusion, Dr. Ravaud emphasizes that we have no reliable or validated signatures to drive clinical decision making at this time. Thus, despite recent breakthroughs in the treatment of patients with first-line metastatic RCC, there remains a large need for studies of biomarker or signature focused trials.


Presented by: Alain Ravaud, MD, PhD, head of medical oncology, Bordeaux University Hospital

Written by: Christopher J.D. Wallis, MD, Ph.D., FRCSC, Instructor in Urology, Vanderbilt University Medical Center, Nashville, Tennessee @WallisCJD on Twitter during the 18th Meeting of the EAU Section of Oncological Urology (ESOU21), January 29-31, 2021

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