Enzalutamide Meets Phase 3 Endpoints in Prostate Cancer

Astellas Pharma and Pfizer recently announced positive results from the phase 3 clinical trial PROSPER, which examined the rate of metastasis among men with non-metastatic castration-resistant prostate cancer (CRPC) treated with enzalutamide (Xtandi), according to a press release.

Enzalutamide is an androgen receptor inhibitor that is indicated to treat patients with metastatic CRPC.

Enzalutamide combined with androgen deprivation therapy (ADT) was observed to decrease the risk of developing metastases or death by 71% compared with ADT alone, according to the press release.

An estimated 164,000 men will be diagnosed with prostate cancer in 2018, making it the second most common cancer in men. Non-metastatic CRPC continues to progress, despite treatments that significantly reduce testosterone levels to resemble castration.

Although there is no evidence of cancer spreading to other parts of the body in patients with non-metastatic CRPC, many of these men will develop metastases in the future, according to the press release.

The randomized phase 3 clinical trial included 1400 patients with non-metastatic CRPC from the United States, Canada, Europe, South America, and the Asia-Pacific region, according to the release.

The trial compared the effects of 160-mg of enzalutamide with placebo. All patients in both treatment arms received ADT, according to the press release.

The primary endpoint of PROSPER was measured by the amount of time until evidence of metastases could be seen in radiographic images, known as metastases-free survival (MFS), or death, within 112 days of ending treatment, according to Astellas.

"In patients with non-metastatic CRPC, there is a high unmet need to delay development of metastases and the progression to advanced prostate cancer. There are currently no approved systemic therapies for patients with non-metastatic CRPC in the US," said researcher Maha Hussain, MD.

Secondary endpoints were the measurements of time until prostate-specific antigen (PSA) progression and the first use of antineoplastic therapy, and the overall survival rate of patients, according to the press release.

Patients who were administered both enzalutamide and ADT had a prolonged median MFS of 36.6, compared with 14.7 months in patients administered ADT monotherapy, according to the study.

Additionally, patients receiving both enzalutamide and ADT had a reduced risk of PSA progression by 93% compared with those treated with ADT monotherapy. The median time until the first use of antineoplastic therapy also increased by 21.9 months in patients administered both treatments, according to the press release.

Overall survival rate could not be determined yet, but the researchers said trends are pointing to an insignificant increase in survival rate among patients who received enzalutamide.

The adverse effects associated with enzalutamide include fatigue, back pain, decreased appetite, constipation, arthralgia, diarrhea, hot flush, upper respiratory tract infections, peripheral edema, dyspnea, musculoskeletal pain, weight loss, headache, hypertension, and dizziness.

Other complications from the trial include seizures and posterior reversible encephalopathy syndrome, and enzalutamide should be discontinued if these reactions occur.

Results of the PROSPER study have been submitted to the FDA, European Medical Association, and other regulatory authorities for review, according to Astellas.

"In the PROSPER trial, treatment with enzalutamide plus ADT delayed the development of metastases compared to standard of care ADT alone and, if approved, may provide men with non-metastatic CRPC an important new treatment option,” Dr Hussain said.