Regulatory Decision Summary for Xtandi

The benefit-risk assessment of Xtandi is considered favourable. The authorization of Xtandi will add a therapeutic option for Canadian men who have asymptomatic or mildly symptomatic metastatic CRPC following failure of androgen deprivation therapy in consideration of its demonstrated survival benefit in these patients, a favourable safety profile (which does not require concomitant use of corticosteroids), and demonstrated tolerability.

In the pivotal study (PREVAIL), statistically significant improvements were demonstrated in co-primary efficacy endpoints of overall survival and radiographic progression free survival (rPFS), as well as all secondary endpoints evaluating time to first skeletal-related event, time to initiation of cytotoxic chemotherapy, time to prostate-specific antigen (PSA) progression, PSA response rate, and best overall soft tissue response. Demonstration of substantial benefit with respect to efficacy in a real-world setting [that is (i.e.) where patients were allowed to receive subsequent therapies with a demonstrated survival benefit] is considered noteworthy. It is considered clinically significant that patients with visceral metastases were included in the study and Xtandi was shown to be as effective in those patients. Treatment with Xtandi was generally well tolerated with a similar percentage of patients in the Xtandi and placebo groups discontinuing treatment as a result of an adverse event. Xtandi therapy was associated with a higher incidence of fatigue, hot flush, hypertension, falls, nonpathological fractures, mental impairment, and neutropenia; all of these adverse reactions had been previously identified. In general, hypertension was not associated with major cardiovascular adverse events. Falls and fall-related injuries, including but not limited to non-pathological fractures, were observed at a greater frequency in the Xtandi arm compared to the placebo arm. More patients in the Xtandi arm versus the placebo arm experienced serious treatment-emergent gastrointestinal bleeding events.

Treatment with Xtandi was not associated with a higher incidence of seizure, hallucinations, or infections leading to death, all previously identified as associated with treatment.

Xtandi does not require the continued use of corticosteroids. Treatment with Xtandi has not been associated with hepatotoxicity or renal toxicity, or with an increased risk of potential hypersensitivity events, or venous thromboembolic events.

The benefit-risk-uncertainty profile of Xtandi for the treatment of asymptomatic or mildly symptomatic CRPC after failure of androgen deprivation therapy is positive and the Product Monograph has been updated with the information supporting its use in these patients. It was noted during the review that patients with clinically significant cardiovascular disease were excluded from the PREVAIL study and the uncertainty of use of Xtandi in these patients has been appropriately addressed with updates to the Product Monograph along with additional information to ensure a positive benefit-risk balance is maintained for this anti-androgen therapy.