The FDA has approved belzutifan (Welireg) for adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), CNS hemangioblastomas, or pancreatic neuroendocrine tumors (pNETS) not requiring immediate surgery.1
The approval was based on data from the phase 2 Study 004, which enrolled patients with VHL-associated RCC, as well as non-renal lesions. Belzutifan induced an objective response rate (ORR) of 49% (n = 30) among 61 patients with VHL-associated RCC. All responses were partial responses.
The median duration of response (DOR) was not reached (range, 2.8+ months to 22+ months). Seventeen responders (56%) had a DOR of at least 1 year. The median time to response was 8 months (range 2.7-19).
Key eligibility criteria for the open-label phase 2 study (NCT03401788) included a confirmed diagnosis of VHL disease (based on germline mutation), at least 1 measurable solid tumor localized to the kidney, and an ECOG performance status of 0 or 1. Prior systemic anticancer therapy was not allowed and patients with metastatic disease were excluded from enrollment.
Overall, the study included 61 patients with a median age of 41 years (range, 19-66). Thirty-two (52.5%) patients were male, and 29 (47.5%) were female. Fifty patients had an ECOG performance status of 0, 10 patients had a performance status of 1, and 1 patient had a performance status of 2. In addition to renal tumors, 24 patients had CNS hemangioblastomas, and 12 patients had pNETs.
Clinical activity with belzutifan was observed in non-RCC lesions. The ORR in pNETS was 83% (n = 10), including 2 complete responses and 8 partial responses. In CNS hemangioblastomas, the ORR was 63% (n = 15), including 1 complete response and 14 partial responses. The median DOR was not reached in either subgroup. The rate of patients with a DOR ≥12 months was 73% and 50% in the CNS hemangioblastomas and pNETS subgroups, respectively.
The safety analysis included all 61 patients. The most common adverse events (AEs) across all grades were anemia (90%), fatigue (64%), headache (39%), dizziness (38%), nausea (31%), constipation (13%), abdominal pain (13%), visual impairment (21%), upper respiratory tract infection (21%), dyspnea (20%), arthralgia (18%), myalgia (16%), hypertension (13%), and increased weight (12%).
Grade 3/4 AEs included anemia (7%), fatigue (5%), hypertension (3.3%) visual impairment (3.3%), dyspnea (1.6%), and increased weight (1.6%).
The FDA noted in a press release, “The use of erythropoiesis stimulating agents for treatment of anemia is not recommended in patients treated with belzutifan.”
References
1. FDA approves belzutifan for cancers associated with von Hippel-Lindau disease. Published online August 13, 2021. Accessed August 13, 2021. https://bit.ly/3fY5JEw.
Adding nivolumab to low-dose tivozanib does not improve PFS in renal cell carcinoma
July 19th 2024"While the addition of an ICI to low dose FOTIVDA did not improve PFS outcomes after prior ICI, we consider the control arm data an important, evidence-based and clinically meaningful contribution to the oncology community treating relapsed or refractory advanced RCC following front-line ICI combinations," says Michael P. Bailey.
Live bacterial supplementation may improve TKI-based treatment efficacy in kidney cancer
June 30th 2024CBM588 could be exciting in cancer treatment because of its potential to enhance the efficacy of immune checkpoint inhibitor-based treatment, improve patient outcomes, and modulate the gut microbiota in beneficial ways,” says Sumanta Pal, MD.
Pembrolizumab/lenvatinib labels updated to include KEYNOTE-B61 data in non-ccRCC
June 28th 2024"The addition of efficacy data from the KEYNOTE-B61 trial reinforces the important role of KEYTRUDA plus LENVIMA as a frontline treatment option for adult patients with advanced RCC regardless of histology," says Takashi Owa, PhD.