by Dana-Farber Cancer Institute

Credit: Unsplash/CC0 Public Domain

Immunotherapies, such as anti-PD-1 and anti-PD-L1, have become standard first line therapies for patients with advanced renal cell carcinoma (kidney cancer). Most patients, however, eventually experience disease progression, with no consensus on what therapy to use next.

In an open-label phase 2 study, led by Dana-Farber Cancer Institute's Toni Choueiri, MD, researchers investigated for the first time the combination of cabozantinib, a VEGF TKI, plus belzutifan, a HIF-2α inhibitor. Belzutifan has shown antitumor activity and favorable safety in heavily pretreated advanced kidney cancer.

The researchers previously reported results for cohort 1 of the trial, called LITESPARK-003. This study reports on cohort 2, which includes patients diagnosed with advanced clear cell renal cell carcinoma who have previously received immunotherapy and up to two systemic treatment regimens. The research is published in The Lancet Oncology journal.

After a median follow-up of 24 months, interim results of the combination show promising antitumor activity in this pretreated patient group with a disease control rate of 92% and a manageable safety profile.

While immunotherapy has changed the treatment landscape for advanced renal cell carcinoma, questions about what therapy to provide when patients experience disease progression on immunotherapy remain. In this study, interim results of the combination of cabozantinib, a VEGF TKI, plus belzutifan, a HIF-2α inhibitor, show promising anti-tumor activity in this pre-treated patient group. The results suggest that the combination might fill and unmet need and provides a rationale for further study of combining a VEGF TKI and a HIF-2 inhibitor.

More information: Toni K Choueiri et al, Belzutifan plus cabozantinib for patients with advanced clear cell renal cell carcinoma previously treated with immunotherapy: an open-label, single-arm, phase 2 study, The Lancet Oncology (2023). DOI: 10.1016/S1470-2045(23)00097-9

Journal information: Lancet Oncology 

Provided by Dana-Farber Cancer Institute