Formal discussant of this trial of MK-6482, Daniel Geynisman, MD, of Fox Chase Cancer Center, Philadelphia, was enthusiastic about this presentation. “The response rates were fabulous in this group of heavily pretreated patients,” he stated. “A total of 69% had some tumor shrinkage, 24% had an objective response, and the disease control rate was 80%. The drug helped all risk groups. The toxicity data were favorable.”
Daniel Geynisman, MD
Dr. Geynisman continued: “Of note, many side effects seen with other tyrosine kinase inhibitors were not prominent with MK-6482. Across all patients treated with hypoxia-inducible factor (HIF)-2a inhibitors, I see consistent results.”
‘Clearly a New Target’
The phase III trial that has been activated will randomly assign 736 patients with no more than three prior therapies to receive either MK-6482 or everolimus. “In this disease setting, everolimus has an objective response rate of 5% and a progression-free survival of 4.4 months. If MK-6482 performs as expected, I hope we will be able to stop this trial early and get this drug to our patients sooner,” commented Dr. Geynisman.
“The question is why use a VEGFR inhibitor if you can inhibit tumor growth more proximally with an agent like MK-6482,” he asked. “This study will not change my practice [today], but HIF-2a is clearly a new target in clear cell renal cell carcinoma.”
DISCLOSURE: Dr. Geynisman has served as a consultant or advisor to AstraZeneca, Eisai, Exelixis, Pfizer, and Seattle Genetics/Astellas and has received institutional research funding from Astellas Pharma, Calithera Biosciences, Genentech, and Merck.
