Belzutifan: enhancing the blockade of angiogenesis in renal cell carcinoma

In The Lancet Oncology, Toni K Choueiri and colleagues 1 Choueiri TK McDermott DF Merchan J 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. Lancet Oncol. 2023; (published online March 31.)https://doi.org/10.1016/S1470-2045(23)00097-9 Summary Full Text Full Text PDF Scopus (8) Google Scholar report the findings from cohort 2 of a phase 2 trial of belzutifan plus cabozantinib in patients with renal cell carcinoma who had previously received an with one previous immune checkpoint inhibitor (28 [54%] of 52 patients enrolled) or immunotherapy and an anti-VEGF or anti-VEGFR tyrosine-kinase inhibitor (24 [46%]). The results were promising, with a confirmed objective response rate of 30·8% (95% CI 18·7–45·1). 1 Choueiri TK McDermott DF Merchan J 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. Lancet Oncol. 2023; (published online March 31.)https://doi.org/10.1016/S1470-2045(23)00097-9 Summary Full Text Full Text PDF Scopus (8) Google Scholar The additional effect of belzutifan is highlighted by the indirect comparison with the phase 3 METEOR trial, 2 Choueiri TK Escudier B Powles T et al. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2016; 17: 917-927 Summary Full Text Full Text PDF PubMed Scopus (709) Google Scholar in which cabozatinib had an objective response rate of 17% (95% CI 13–22) in patients pretreated with tyrosine-kinase inhibitors. Moreover, in Choueiri and colleagues' study, the short median time to response (3·2 months [IQR 1·9–7·3]) and number of patients with a change from baseline in the diameter of target lesions (45 [87%]) are two endpoints that support the pivotal role of enhancing the blockade of angiogenesis to achieve satisfactory disease control. Belzutifan plus cabozantinib for patients with advanced clear cell renal cell carcinoma previously treated with immunotherapy: an open-label, single-arm, phase 2 studyBelzutifan plus cabozantinib has promising antitumour activity in patients with pretreated clear cell renal cell carcinoma and our findings provide rationale for further randomised trials with belzutifan in combination with a VEGFR tyrosine-kinase inhibitor. Full-Text PDF