Invited discussant David A. Braun, MD, PhD, of Dana-Farber Cancer Institute, Boston, said there are a couple of established pillars of systemic therapy for metastatic renal cell carcinoma (RCC). “An immune checkpoint inhibitor is a strong pillar, a [vascular endothelial growth factor tyrosine kinase inhibitor] is a strong pillar, and there is a critical need for novel targets to make an additional pillar of effective therapy.”

“Belzutifan blocks binding of hypoxia-inducible factor–2α to its partner ARNT (hypoxia-inducible factor 1β) in the “pseudohypoxic” conditions of clear cell RCC that can lead to downstream growth and the development of RCC. This seems like a great way to target the underlying pathobiology of clear cell RCC,” he commented.

The abstracts presented at the 2021 Genitourinary Cancers Symposium focused on the following questions: Is belzutifan safe, does it have a signal for antitumor activity, and can it be safely and effectively combined with cabozantinib? “To answer the first question, belzutifan does appear to be safe. The most common adverse events were on-target effects. It’s encouraging that there were no grade 4 or 5 events and few unmanageable side effects. While we await results of the phase III trial, the initial answer appears to be yes, it seems to be a safe monotherapy,” Dr. Braun stated.

“There was a signal for antitumor efficacy as well,” he continued. “The majority, 64%, had some tumor shrinkage, and 80% had disease control (response or stable disease). For responders, the median duration of response was not reached with at least 2 years of follow-up. Progression-free survival was encouraging in intermediate- and poor-risk patients and in heavily pretreated patients.” 

David A. Braun, MD, PhD

Comments on the Combination

Turning to Dr. Choueiri’s abstract, it appears that the combination of belzutifan plus cabozantinib is safe and potentially effective in the post–immune checkpoint inhibitor setting, he continued, but he cautioned that the data are preliminary.

“The median follow-up was only about 11 months, and the minimum follow-up was only 5.6 months. This is interesting and potentially exciting, but we really need to have further follow-up. When we look at the progression-free survival curve, which looks impressive, it’s a median of 16.8 months. But, again, very few patients are out that far. It’s definitely very preliminary,” he commented.

“It may be an effective regimen, but it is too soon to tell,” he added. “While these abstracts will not change practice on Monday morning after this conference, they give us several reasons for excitement.”

DISCLOSURE: Dr. Braun has received honoraria from LM Education/Exchange Service; has served as a consultant or advisor to Adept Field Solutions, Blueprint Partnerships, Bristol Myers Squibb, Charles River Associates, Dedham Group, Defined Health, Insight Strategy, Octane Global, Schlesinger Associates, Slingshot Insights, and Trinity Group; and has been reimbursed for travel, accommodations, or other expenses by Bristol Myers Squibb.