Major Breakthrough: New Class of Anti-Cancer Drug Effective Against Kidney Cancer

By Annette M. Boyle, /alert Contributor
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Five year survival rates for metastatic renal cell carcinoma remain abysmal at just 10%, despite development in recent years of more than a dozen therapies. Researchers at the University of Texas (UT) may have found a new class of drugs that can break through the barriers to long-term remission or a cure for this challenging form of cancer.

The Texas team has been working with PT2385, an antagonist of hypoxia inducible factor-2α (HIF-2α), a transcription factor that promotes tumorigenic pathways. Previous research demonstrated that PT2385 reduced the growth of half of kidney cancers implanted in mice. The current study, published in the December issue of the Journal of Clinical Oncology, found that the agent stopped renal cell tumor growth for more than four months in 40% of patients and for more than 12 months in 25% of patients, while causing minimal adverse effects.


Metastatic renal cell carcinoma. (Source: Creative Commons)

“This HIF-2α inhibitor offers a combination of safety and potential activity that is unique compared to current treatments for advanced kidney cancer,” corresponding author Kevin Courtney, MD, corresponding author and assistant professor of internal medicine, hematology and oncology at UT Southwestern’s Harold C. Simmons Comprehensive Cancer Center in Dallas, said in a press release. Patients received doses ranging from 100 to 1800 mg twice a day, with an expansion phase at the recommended phase II dose of 800 mg twice per day.

The phase I study enrolled 51 patients with locally advanced or metastatic clear cell renal cell carcinoma (ccRCC) who had experienced progression on one or more previous regimens that included a vascular endothelial growth factor (VEGF) inhibitor. Participants had received an average of four prior therapies. Of the 51 patients, 26 participated in the dose-escalation phase and 25 in the study’s expansion phase.

Objective response rate was 14% with 2% of patients achieving complete response and 12% obtaining partial response. In addition, 52% of the participants experienced stable disease following therapy. The researchers observed that “greater exposure seemed to be correlated with longer PFS [progression-free survival].”

No patients experienced dose-limiting toxicity at any of the tested doses. The most serious adverse effects that took place were grade 3 asymptomatic anemia (10%), hypoxia (10%), hypophosphatemia (8%) and lymphopenia (4%, grade 3 and 4% grade 4). 

“PT2385 showed promising efficacy in a highly pretreated patient population (31% of patients received five or more prior therapies),” the authors wrote. They also noted that their results were particularly encouraging given that other phase I studies of targeted agents in this population resulted in dose reduction or discontinuation in a large percentage of the study group.

In contrast, only two patients receiving PT2385 required dose reduction and no participants in this study discontinued because of adverse effects. Further, 21 patients had stable disease or response for more than four months, 13 patients continued in the study for more than one year, and one patient who previously received sunitinib and temsirolimus achieved complete response and was continuing treatment after more than two years on the new drug.


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