At first, the drugs abiraterone and enzalutamide were thought to be rivals, competing over how to best thwart androgen-receptor driven, castrate-resistant prostate cancer. But MD Anderson prostate cancer researchers found instead that they’re powerful allies for some patients.
Based on earlier studies that showed certain patients treated with the two drugs achieved a pathological complete response, a phase II combination clinical trial was launched under the auspices of the Prostate Cancer Moon Shot. Christopher Logothetis, M.D., calls it “the first intent-to-cure clinical trial for prostate cancer.”
The two drugs target the androgen receptor testosterone pathway in different ways to reduce levels of the male hormone, which fuels most prostate cancers. Both are approved by the FDA as single agents for prostate cancer, but cancers eventually become resistant to them.
So far, 128 eligible patients are enrolled in the 180-patient phase II study.
Logothetis, chair of Genitourinary Medical Oncology, and colleagues found that the drug combination stops the resistance that develops to either drug alone. Their findings inspired a national phase III clinical trial of the combination, even before the completion of the phase II trial.
The endpoint of the trial will be progression-free survival two years after patients’ testosterone returns to normal levels.
It fits into a larger theme of identifying biomarkers to more effectively guide treatment with available drugs. In addition to pinpointing patients who need anti-hormonal drugs, the team also found that 30% of patients were resistant to these options and, therefore, are better treated with chemo.
“We now know how to select those who need each type of therapy, have markers and models to reflect that, and have designed and gained approval of a clinical trial to integrate those concepts,” Logothetis says. “We’ve done that in a year.”