FDA Approves Xtandi for Non-Metastatic Castration-Resistant Prostate Cancer

The Food and Drug Administration (FDA) has approved Xtandi (enzalutamide) for the treatment of patients with non-metastatic castration-resistant prostate cancer (CRPC), according to Pfizer and Astellas, the manufacturers of the drug. That means it will treat disease that has not spread outside the prostate gland, but is progressing despite therapy that has deprived the body of the hormone testosterone, which drives the disease.

Xtandi, an androgen receptor inhibitor that prevents the body from using any testosterone or other cancer-driving hormones that are present, had previously been approved to treat metastatic CRPC, disease that has spread to other parts of the body. This makes it the only oral medication approved to treat both non-metastatic and metastatic CRPC.

The approval is based on findings from the phase 3, double-blind PROSPER trial, which showed that Xtandi lowered the risk of metastasis or death in patients who took it along with androgen-deprivation therapy (ADT). The study found that patients who took both drugs went a median of 36.6 months before developing metastases, while those taking Xtandi alone went 14.7 months before experiencing disease spread. A total of 1,401 patients participated in the study, with twice as many patients receiving the two-drug combination as ADT alone.

The study also measured the time until patients needed to start another anti-cancer therapy, which was 39.6 months for those who took the combination versus 17.7 months for those who took ADT alone. Data about how the two drug regimens affected overall survival were not yet available at the time of the study’s final analysis.

“As the leader of the foundation that funded the initial synthesis and early development of this class of drug developed for the treatment of advanced disease, it is rewarding to see the progression of the science evolve into what is now a treatment for a previously unmet need — a treatment for men who are in the “empty spaces” between the failure of androgen deprivation therapy resulting in CRPC and the onset of metastatic disease,“ said Jonathan Simons, M.D., Prostate Cancer Foundation President and CEO.

It should be noted, however, that the men in the Xtandi arm had more side effects compared with their counterparts who took ADT alone. The most common side effects that occurred more in the Xtandi arm than in the ADT-alone arm included weakness, hot flush, high blood pressure, dizziness, nausea and falling. Serious or severe side effects were experienced by 31 percent of men in the Xtandi arm and 23 percent of those in the ADT-only arm. Data submitted prior to March 2018, when Xtandi was given priority review designation by the FDA, showed that the most common serious and severe side effects patients had experienced were hypertension and fatigue.

Furthermore, 3.4 percent of patients in the Xtandi group and 0.6 percent in the ADT monotherapy group died from side effects. Patients who dropped out of the trial citing a side effect as the primary reason comprised 9.4 percent of the group treated with Xtandi versus 6 percent of the men treated with only ADT.

Xtandi was initially approved in 2012 to treat men with metastatic CRPC after they’ve been treated with docetaxel. Two years later, in 2014, the approval was expanded to men with metastatic CRPC who have not been treated with chemotherapy.

“With today’s approval, there is now a new option for patients with non-metastatic CRPC that could lead to better outcomes, including longer survival and delayed onset of symptoms,” Simons said.