Combination therapy a promising option for advanced kidney cancer patients already treated with immunotherapy
Study Title: Belzutifan plus cabozantinib for patients with advanced clear cell renal cell carcinoma previously treated with immunotherapy: an open-label, single-arm, phase 2 study
Publication: The Lancet Oncology, March 31, 2023, 6:30pm ET https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(23)00097-9/fulltext
Dana-Farber Cancer Institute author: Toni K. Choueiri, MD
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 this 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. After a median follow-up of 24 months, interim results of the combination show promising antitumor activity in this pre-treated 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.
Funding: Merck Sharp & Dohme (a subsidiary of Merck & Co) and the National Cancer Institute.