Results of a phase III clinical trial of the drug Enzalutamide, published yesterday in the New England Journal of Medicine, show the drug extends life by an average five months in the most advanced stages of prostate cancer.
"This is a major advance. Not only do we see more survival benefit than from traditional chemotherapy, but the side effects of Enzalutamide are much lower. It provides both more benefit and less harm - you get the quantification of more life, but also see quality of life improvements," says study co-author, Thomas Flaig, MD, medical director of the University of Colorado Cancer Center's Clinical Investigations Shared Resource and associate professor of medicine at the University of Colorado School of Medicine.
The study, known by the acronym AFFIRM, followed 1199 patients with prostate cancer that had progressed despite both hormonal and chemotherapy treatments, with 2/3 of patients receiving the drug Enzalutamide versus control. Median overall survival for patients in the treatment arm of the trial was 18.4 months compared to 13.6 months for patients in the placebo arm. In addition to prolonged survival, patients given Enzalutamide showed meaningful improvement in other measures including PSA blood levels, an increase from 3.0 months to 8.3 months in time until PSA progression, and an increase from 2.9 months to 8.3 months in overall progression-free survival.
The once-a-day oral drug works by blocking prostate cancer's ability to supply itself with androgens - hormones including testosterone that otherwise drive the cancer's growth. It does this by binding to cancer cells' androgen receptors - the waving tentacles on the outsides of cells that are designed to grab specific molecules as they float past. Enzalutamide plugs these receptors, removing their ability to grab androgen.
This out-competition for space in androgen receptors is not a new strategy. But when treated with existing anti-androgen drugs, prostate cancer tends to pull androgen receptors inside the cell walls, into a cell's nucleus where the receptors are shielded from drugs but can continue to trap androgens and thus signal growth. In addition to plugging receptors, Enzalutamide inhibits this nuclear translocation.