Dr Garmezy on Considerations For Frontline Treatment Selection in ccRCC

Benjamin Garmezy, MD, medical oncologist, assistant director, Genitourinary Research, Sarah Cannon Research Institute, Tennessee Oncology, discusses key considerations for the selection of frontline treatment regimens in clear cell renal cell carcinoma (RCC).

The choice between an immunotherapy doublet consisting of a PD-1 inhibitor and a CTLA-4 inhibitor vs a combination of animmunotherapy agent in combination with a VEGF-targeted TKI in the frontline setting for patients with ccRCC is influenced by several key factors, Garmezy begins.

Sarcomatoid features serve as a rationale for opting for an immunotherapy doublet, he states. For younger patients who do not require a rapid response and are seeking enhanced durability, immunotherapy doublets may be considered, Garmezy adds. Conversely, an immuno-oncology (IO)/TKI regimen may be ideal for patients who prioritize a rapid response, he says.

In the absence of sarcomatoid features, Garmezy is increasingly selecting IO/TKI combinations for patients with RCC. There are currently 3 approved regimens for these patients: pembrolizumab (Keytruda) and axitinib (Inlyta), pembrolizumab and lenvatinib (Lenvima), and cabozantinib (Cabometyx) and nivolumab (Opdivo), Garmezy details. Although these combinations share more similarities than differences, choosing among them can be complex, he says. Garmezy recommends starting with 1 combination, familiarizing oneself with its toxicity profile, dose reductions, and interruptions to effectively manage patient adherence.

Notable nuances include axitinib’s higher VEGF selectivity compared with the more multi-targeted TKIs cabozantinib and lenvatinib, Garmezy details. Axitinib’s shorter half-life may be advantageous in cases where concerns exist about patient reactions to the drug, he suggests. However, pembrolizumab and lenvatinib have demonstrated the highest response rates, Garmezy says, cautioning that cross-study comparisons are challenging due to differing trial populations. Overall, this evolving landscape underscores the need for a personalized approach, considering patient characteristics, preferences, and potential toxicities to optimize treatment outcomes, Garmezy concludes.