Belzutifan shows strong clinical activity in two rare neuroendocrine tumors

Belzutifan shows strong clinical activity in two rare neuroendocrine tumors

A multicenter Phase II clinical trial led by researchers at The University of Texas MD Anderson Cancer Center demonstrated significant tumor shrinkage and disease control in patients with advanced pheochromocytoma and paraganglioma (PPGL), two rare and potentially life-threatening neuroendocrine tumors.

The results of this study led by Dr. Camilo Jimenez, Professor of Endocrine Neoplasia and Hormonal Disorders, were published today in theNew England Journal of Medicineand simultaneously presented at the European Society for Medical Oncology (ESMO) Congress 2025 (Abstract 1705O).

What was the main result of the study?

The study showed that the HIF-2α inhibitor belzutifan demonstrated significant antitumor activity with an objective response rate of 26%, a significant achievement particularly in rare and difficult-to-treat cancers. These effects lasted on average for more than 20 months, indicating sustained clinical benefit for those who responded to treatment.

Notably, nearly a third of patients (32%) taking blood pressure medications were able to reduce their dosage by half for at least six months. This is an important finding because PPGL tumors often produce excess hormones that increase blood pressure. These results suggest that belzutifan may also have contributed to the relief of symptoms associated with hormone-secreting tumors.

The primary significance of this study is to demonstrate that HIF-2α inhibition with belzutifan can provide significant clinical benefit in patients with advanced, progressive PPGL. In a population with no remaining standard care options, we observed durable disease control and a manageable safety profile, supporting the rationale for HIF-2α as a therapeutic target in this rare tumor type.”

Camilo Jimenez, MD, professor of endocrine neoplasia and hormonal disorders

Why is the LITESPARK-015 study important?

Pheochromocytomas and paragangliomas (PPGL) are difficult-to-treat cancers that affect approximately 2,000 people annually in the United States. One of the main drivers of tumor growth in PPGL is the HIF-2α protein. In healthy cells, this protein adapts to changes in oxygen levels, but genetic mutations or changes in cell metabolism can cause HIF-2α to become abnormally active, triggering signals that help the tumor grow and spread.

HIF-2α inhibitors such as belzutifan have been successful in shrinking tumors and slowing disease progression in other cancers caused by HIF-2α overactivity, such as kidney cancer and von Hippel-Lindau disease (VHL). Building on this knowledge, researchers evaluated the effectiveness of these inhibitors in patients with advanced PPGL.

In the phase II LITESPARK-015 trial, 72 patients with locally advanced, metastatic, unresectable PPGL who had exhausted all other standard treatments were treated with belzutifan.

Is belzutifan approved for the treatment of PPGL?

In May 2025, the Food and Drug Administration (FDA) approved belzutifan for the treatment of adult and pediatric patients 12 years of age and older with advanced, unresectable or metastatic PPGL who do not require immediate surgery. Belzutifan is the first oral and only approved therapy for this disease, representing a new standard of care for this patient group.

"The approval of belzutifan provides new hope. As an oral treatment, it has been shown to shrink tumors, relieve symptoms and improve quality of life with low toxicity. It represents a significant advance in the care of people with these rare cancers," Jimenez said.

Timeline

2025 – FDA approves belzutifan for the treatment of adult and pediatric patients 12 years of age and older with PPGL

2023 - FDA approves belzutifan for advanced renal cell carcinoma (RCC) following treatment with a PD-1/PD-L1 inhibitor and a VEGF tyrosine kinase inhibitor (VEGF-TKI)

2021 - FDA approves belzutifan for adults with von Hippel-Lindau (VHL) disease who require treatment for associated tumors (RCC, central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors) when surgery is not immediately necessary

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