FDA Expands Xtandi Approval to Include Metastatic Castration-sensitive Prostate Cancers

The U.S. Food and Drug Administration (FDA) has agreed to expand Xtandi‘s (enzalutamide) approval to include men whose metastatic prostate cancer still responds to hormone therapy, Astellas Pharma and Pfizer, the treatment’s developers, announced.

The recent approval, which covers men with metastatic castration-sensitive prostate cancer (mCSPC), follows approvals for non-metastatic and metastatic castration-resistant prostate cancers, making Xtandi the first oral treatment approved in the U.S. for these three types of advanced prostate cancer.

“Xtandi has been established as a standard of care for men with castration-resistant prostate cancer and has been prescribed to more than 420,000 patients worldwide since it was first approved in 2012,” Andrew Krivoshik, MD, PhD, senior vice president and oncology therapeutic area head at Astellas, said in a press release. “This approval in metastatic castration-sensitive prostate cancer means physicians can now offer Xtandi to men earlier in their advanced prostate cancer treatment journey.”

Metastasis is a major cause of complications and death among men with prostate cancer. Once prostate cancer spreads, patients tend to have a poor prognosis, even if their cancer still responds to hormone therapy.

Xtandi is a form of hormone therapy that aims to prevent male hormones from sending chemical signals that stimulate cancer growth; it does so by blocking the activity of their receptor. The treatment was developed for advanced forms of prostate cancer.

The decision to approve Xtandi for men with mCSPC was based on data from the ARCHES Phase 3 trial (NCT02677896), where a combination of Xtandi and standard androgen deprivation therapy (ADT) lowered the risk of radiographic disease progression by 61%, compared to ADT plus a placebo.

The multinational ARCHES trial included 1,150 patients across the U.S., Canada, Europe, South America, and the Asia-Pacific region, who were randomly assigned Xtandi or a placebo.

Participants could be either newly diagnosed with metastatic disease or have received prior therapy and subsequently developed metastasis. They all continued to receive ADT — in the form of a luteinizing hormone-releasing hormone agonist or antagonist — unless they had had a bilateral orchiectomy (surgery to remove both testicles).

ARCHES’ main goal was radiographic progression-free survival (or the time to first evidence of radiographic disease progression) or death within 24 weeks of treatment discontinuation, whichever came first.

Secondary objectives included overall survival, time to a skeletal event — bone disease, radiation to the bone, or spinal cord compression — time to PSA progression, time to a new anti-cancer treatment, and objective response rate.

In addition to delaying radiographic disease progression, the treatment also reduced the risk of PSA progression by 81% and the chance of starting a new anti-cancer treatment by 72%, compared to ADT alone. As a majority of patients on both arms were alive at the time of the analysis, researchers haven’t been able to determine if Xtandi also extends patient survival.

Adverse events in ARCHES were similar to those seen in other trials of Xtandi in castration-resistant prostate cancer patients. Adverse events more frequently reported with Xtandi than placebo included hot flashes, fatigue, joint pain, high blood pressure, fractures, and muscle pain.

“Men with metastatic castration-sensitive prostate cancer face complex treatment decisions and it is critical for physicians and patients to have as much information as possible when deciding on all of the options available,” said Andrew Armstrong, MD, Duke University professor, director at Duke Cancer Institute, and lead investigator of ARCHES. “The research supporting the FDA approval and updated treatment guidelines provide physicians and patients with compelling evidence to consider enzalutamide as a treatment option for men with this disease.”

Andy Schmeltz, global president of Pfizer Oncology, said: “Today’s approval adds to over a decade of global clinical research aimed at better understanding the potential benefit of Xtandi for men with advanced prostate cancer. The FDA approval marks continued progress to help meet the needs of patients, including men living with metastatic castration-sensitive prostate cancer.”

Pfizer and Astellas are also providing information and assistance to patients eligible to receive Xtandi. The companies have included information on insurance benefits and financial assistance on the treatment’s website.

An ongoing Phase 3 trial — called EMBARK (NCT02319837) — is now testing Xtandi on prostate cancer patients with hormone-sensitive disease that has not yet spread beyond the prostate, the results of which may help extend Xtandi’s indication to all castration-sensitive patients.