Adding Xtandi to Xofigo Does Not Raise Risk of Bone Issues in CRPC, Study Says

Metastatic castration-resistant prostate cancer (CRPC) patients who receive Xtandi (enzalutamide) plus Xofigo (radium-223) in a real-world setting do not experience more fractures or bone-related events than those given Xofigo alone, an observational study shows.

This has been a common concern for metastatic CRPC patients, among whom Xofigo is associated with an increased risk of fractures, particularly when used in combination with other treatments such as  Zytiga (abiraterone acetate) and glucocorticoids.

The findings were presented at the 2019 Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting, June 22–25 in Anaheim, California, in a study titled, “Co-treatment with Radium-223 and Enzalutamide: Outcomes in Patients with Metastatic Castration-Resistant Prostate Cancer (mCRPC) from a Prospective Multicenter Observational Study.”

Xofigo, by Bayer, is a kind of internal radiation therapy indicated to treat bone metastasis in prostate cancer patients who no longer respond to hormone therapies — a population with castration-resistant prostate cancer.

In combination with other treatments, the therapy significantly extended overall survival and delayed the first bone-related events, compared to a placebo, in metastatic CRPC patients. But when the treatment was tested in combination with Zytiga and prednisone — a standard approach for mCRPC patients — data indicated more bone fractures in study participants.

Xtandi is another prostate cancer therapy that, like Zytiga, targets the androgen inhibitor and reduces cancer growth in mCRPC patients. Thus, researchers aimed to investigate the safety of Xtandi plus Xofigo in routine clinical practice.

The non-interventional, prospective study — called REASSURE (NCT02141438) — included 1,439 patients with metastatic CRPC who received Xofigo alone or Xofigo plus Xtandi based on their doctor’s decision.

The study included three groups of patients: those who received Xofigo only (763 patients), those who initiated Xofigo and Xtandi within 30 days of each other (47 patients; the concurrent group), and those who initiated one of the two medicines more than 30 days after first treatment with the other (220 patients, the layered group). Patients were followed for a median of 9.1 months.

Researchers evaluated the rate of bone events — deemed as fractures, bone surgery, spinal cord compression, radiotherapy to relieve bone symptoms, and progression of bone metastasis — as well as the use of bone health agents and overall survival.

Overall, 17% of patients experienced a bone event during the study, including 17% of those on Xofigo only, 9% of those on the concurrent treatment regimen, and 16% of those receiving the layered treatment.

Fractures, specifically, did not affect any patient in the concurrent group, but occurred in 2% of those on Xofigo only, and in less than 1% of those on the layered treatment.

The median overall survival was 19.7 months in patients in the concurrent group, 15 months in the layered group, and 15.8 months in the Xofigo only group. However, patients in the concurrent treatment group may have had a less advanced prostate cancer, as a smaller proportion had previously received chemotherapy, researchers said.

The combination is now being examined in a randomized, controlled setting in the ongoing PEACE III Phase 3 trial (NCT02194842). The study is recruiting mCRPC patients with symptomatic or mildly symptomatic bone metastasis to determine whether a combination of Xtandi plus Xofigo is better than Xtandi alone at extending the time patients live without developing new bone metastasis or seeing their metastasis progress.