Dr Jonasch on the Evolution of Belzutifan in Cancer Care

Eric Jonasch, MD, professor, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the evolution of belzutifan (Welireg) in cancer care, highlighting the agent’s potential for the treatment of patients with renal cell carcinoma (RCC).

At the 2023 International Kidney Cancer Symposium (IKCS), Jonasch delivered a presentation focusing on the narrative surrounding belzutifan. Belzutifan is a HIF2α inhibitor that originated from research conducted at UT Southwestern Medical Center following foundational work across various global locations, he begins. The early development of this agent led to the establishment of a company that produced 2 compounds: PT-2385 and, ultimately, belzutifan, which gained FDA approval in 2021 for adult patients with von Hippel-Lindau disease who require therapy for associated cancers, Jonasch explains. Phase 3 data from the LITESPARK-005 trial (NCT04195750) presented at the 2023 ESMO Congress indicate a potential registrational path for belzutifan for patients with advanced RCC who have undergone prior therapy, he emphasizes.

The development of belzutifan is particularly thrilling for the RCC field as, until now, treatment options were limited to checkpoint-blocking antibody therapy and anti-angiogenic TKIs, Jonasch continues. Belzutifan introduces a mechanism of action that is unique yet complementary to the mechanisms of other agents used in RCC. The activity of belzutifan is evident in the subset of patients experiencing profound benefits with the drug, which is also well tolerated in these populations, he explains. Ongoing investigations involve exploring the combination of belzutifan with anti-angiogenic agents and immune checkpoint–blocking antibody therapy, with forthcoming data expected to guide optimal usage of this agent, Jonasch emphasizes.

Looking ahead, the envisioned future for RCC management with belzutifan includes the regulatory approval of this agent for patients with advanced RCC and its potential integration into earlier lines of treatment, he expands. The prospect of using belzutifan, either as monotherapy or in combination with other agents, seems promising for patients with favorable- or intermediate-risk disease. The goal is to advance belzutifan into earlier treatment stages, augmenting the outcomes achieved with existing agents, Jonasch concludes.