Results from a trial of the anticancer drug galeterone show that it is successful in lowering prostate-specific antigen (PSA) levels in men with castration-resistant prostate cancer (CRPC). These results were presented at the 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, in Barcelona, Spain.

Galeterone was well tolerated by patients in the ARMOR2 trial, and also lowered PSA levels in a subset of men with CRPC that was resistant to other drugs that target the cancer, such as enzalutamide and abiraterone. These results were presented by associate professor Mary-Ellen Taplin, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts.

“Recent data have shown that a variant of the androgen receptor called AR-V7, found in tumor cells circulating in the blood of patients with metastatic CRPC, predicted resistance to treatment with enzalutamide and abiraterone,” said Taplin. “Indeed, we believe AR-V7 and other, related variants are a mechanism of resistance in this disease and patients who have them may have a poorer prognosis.”

Continue Reading

Several clinical centers in the United States and Canada recruited four groups of men with CRPC to a phase II study to receive 2,550 mg of galeterone orally once a day: 22 men had CRPC that had not metastasized and had received no previous treatment; 39 men had metastatic CRPC and no previous treatment with abiraterone or enzalutamide; and nine men had metastatic CRPC and had failed treatment with abiraterone and enzalutamide respectively.

As well as evaluating PSA responses to the drug, the researchers also analyzed levels of circulating tumor cells, including identifying whether or not they contained the AR-V7 variant. Circulating tumor cell numbers were higher in patients who had received more prior therapies. Among the seven patients who were likely to have the AR-V7 variant, six had favorable responses to galeterone, suggesting that the presence of AR-V7 does not preclude response to the drug.

“We found that galeterone resulted in meaningful PSA declines in patients with metastatic CRPC, and imaging showed that the disease was stable or had responded to the drug,” said Taplin. “Galeterone was safe, without any unexpected toxicity.”

Among the group of 60 men who had nonmetastatic and metastatic disease who had not received prior treatment with abiraterone and enzalutamide, PSA levels declined by 30% or more (PSA30) in 50 of 60 (83%) patients, of whom 42 (70%) went on to have declines of 50% or more (PSA50). Among patients who were resistant to abiraterone, 13 of 37 (35%) had any PSA decline. Among the nine evaluable patients who were resistant to enzalutamide, 5 of 9 (56%) had any PSA decline.

The presence of circulating tumor cells were evaluated in 71 patients and were found to be higher in 64 (90%) of the patients who had more advanced cancer that had failed more previous treatments.

Galeterone will now be tested in a phase III trial in which patients with metastatic CRPC with the AR-V7 variant will be randomized to receive either galeterone or enzalutamide.