FDA approves new drug for men at high risk of prostate cancer spread

A newly approved drug called apalutamide is giving hope to thousands of men confronting a tenacious problem after being treated for prostate cancer. Prostate-specific antigen (PSA) levels should plummet to zero after surgery, and to near zero after radiation therapy, but in some men, they continue rising even when there’s no other evidence of cancer in the body. Doctors typically respond to spiking PSA with drugs that block the production of testosterone, which is the male sex hormone that fuels prostate cancer. However, this type of medically induced castration, called hormonal therapy, doesn’t always reduce PSA. Moreover, prostate cancer cells can become resistant to hormonal therapy, after which PSA resumes its upward march. This is called non-metastatic castration resistant prostate cancer (nmCRPC), and it often precedes the appearance of metastatic tumors that show up later.

The dearth of approved treatments for nmCRPC has long frustrated patients and their doctors alike. But in February, the US Food and Drug Administration approved apalutamide for men who have nmCRPC after results from the SPARTAN clinical trial showed the drug could delay metastases by up to two years. “Based on these clinical trial results, apalutamide should be considered the new standard of care for nmCRPC,” said Dr. Matthew Smith, a medical oncologist at Massachusetts General Hospital who led the study. “The drug addresses a great clinical need and holds the promise of longer survival for men whose cancer defies hormonal therapy.”

The SPARTAN trial enrolled 1,207 men whose PSA levels doubled within 10 months or less after initial treatment despite ongoing hormonal therapy. Enrolled men were assigned to either daily apalutamide tablets combined with hormonal therapy, or to hormonal therapy combined with placebo. Doctors usually stick with hormonal therapy even after PSA levels rise, since it prevents the body from recovering its ability to make testosterone. Men continued on the study until the first metastases were detected, and then they were given other drugs used for treating metastatic prostate cancer.

According to the results, those taking apalutamide avoided metastases for a median of 40.5 months (meaning half were free of metastases for longer than that, and the other half for less). The placebo-treated men, meanwhile, remained free of metastases for a median of 16.2 months, about two years less. Furthermore, apalutamide treatment “delayed symptomatic progression, pain, and other symptoms that patients experience as a consequence of their cancer,” Smith said. But apalutamide, which prevents testosterone from interacting with its receptor on cancer cells, was also associated with more frequent significant side effects, such as fatigue, rash, weight loss, falls, and skeletal fractures.

Based on accumulating evidence, Smith anticipates that longer freedom from metastases equates with longer overall survival in men with nmCRPC. However, whether that’s true remains to be seen. “So far, outcomes suggest men will live longer on apalutamide,” said Dr. Marc Garnick, the Gorman Brothers Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, and editor in chief of HarvardProstateKnowledge.org. “The anxiety most patients experience when PSA increases after what was thought to be curative is significant. Continuing with this new therapy should be considered between appropriately selected patients and their doctors after a full discussion of the potential benefits and risks.”