At the European Society of Medical Oncology (ESMO) Virtual Congress 2020, Dr Cristina Suarez from the Hospital Universitari Vall D’Hebron and Vall D’Hebron Institute of Oncology in Barcelona, Spain presented an update of the clinical data from the phase 2 study of oral HIF-2a MK-6482 in Von Hippel-Lindau disease-associated cancers.
Von Hippel-Lindau disease is a condition associated with inherited alterations in the VHL gene. It results in benign and malignant tumours, including clear cell renal cell carcinoma (RCC). It is very rare and recruitment into clinical trials is difficult. Currently, VHL RCC is managed with surgery; tumours less than 3 cm in diameter are removed to limit the risk of metastatic disease but also avoid renal insufficiency that results from multiple tumours in the kidney for as long as possible.
Inactivation of the VHL gene is thought to partly act through activation of the HIF-2a transcription factor. MK-6482 is an oral inhibitor of HIF-2a. Data from 61 patients treated with MK-6482 were summarised. Overall response rate was 36.1% and 91.8% of tumours reduced in size. No patients to date have progressive disease.
This response rate is comparable to previously reported outcomes with other targeted agents in RCC, such as sunitinib and pazopanib. MK-6482 is also active in other VHL disease-associated tumours such as pancreatic and CNS lesions.
While promising, further study is required to confirm the benefit of MK-6482 in randomised clinical trials and to understand its efficacy in advanced disease, and to see if the drug might be more effective in combination.