Casodex Prostate Cancer Monotherapy Survival Is Similar To Castration - U.K.

Prostate cancer treatment with AstraZeneca's Casodex (bicalutamide) as monotherapy does not increase mortality risk compared to castration, U.K. labeling for the anti-androgen indicates. The Medicines Control Agency cleared the indication on June 17.

"A combined analysis of survival data in patients with non-metastatic disease at entry into two pivotal trials (n=480), with an overall mortality of 42% and median follow-up of five years, showed that there was no significant difference between Casodex and castration in survival," U.K. labeling states. However, equivalence of the two treatments "could not be concluded statistically."

AstraZeneca is touting Casodex as "the first anti-androgen to demonstrate no overall difference in the risk of death compared to castration in prostate cancer as monotherapy."

Launched in the U.K. market on June 22, Casodex 150 mg is indicated for "the management of patients with locally advanced, non-metastatic prostate cancer for whom surgical castration or other medical intervention is not considered appropriate or acceptable."

AstraZeneca noted that "further launches are anticipated during 1999," and said that it plans to file a supplemental NDA with FDA in due course. Casodex is approved in the U.S. as combination therapy with leutinizing hormone-releasing hormone analogue.

The monotherapy indication for Casodex was based on the combined analysis of two randomized trials designed to compare the efficacy, tolerability, and quality of life benefits of bicalutamide 150 mg with castration.

Randomized in a 2:1 ratio, patients in the parallel open trials received oral bicalutamide 150 mg/day or castration with either bilateral orchiectomy or AstraZeneca's Zoladex (goserelin). Primary endpoints of the studies were time to death, objective progression and treatment failure, and quality of life.

Data from the two similarly designed studies were pooled where possible. In trial 306, 86 patients received bicalutamide and 42 received castration, while trial 307 included 234 patients randomized to bicalutamide and 118 to castration.

At a median follow-up of four years, the overall mortality rate was 31%. Casodex 150 mg was determined to be statistically equivalent to castration with regard to mortality. The mortality rate for patients receiving bicalutamide was 30.9% (n=99), compared with 30% (n=48) of castrated patients. Bicalutamide 150 mg yielded a 7% lower risk of death from any cause than that associated with castration.

Disease progression and treatment failure endpoints varied between studies, which prevented combined analysis of the results. Study 306 showed that Casodex increased both time to treatment failure and objective progression. Study 307, however, yielded results favoring castration for both endpoints.

AstraZeneca attributed the contradictory results to variations in disease assessment as well as a potential bias associated with the open nature of the trial. Disease progression, for example, was established by digital rectal examination in 18% of patients in study 306 vs. 37% in study 307.

In the area of treatment failure, trial 306 showed an advantage for bicalutamide: 60.5% of Casodex patients experienced treatment failure, compared to a 73.8% treatment failure rate for the castration arm. In trial 307, castration yielded a 72.9% treatment failure rate vs. an 81.6% failure rate for bicalutamide patients.

Disease progression results from study 306 yielded a 47.7% objective progression rate for Casodex, compared to 64.3% for the castration group. In trial 307, however, the objective progression rate for Casodex was 65% vs. 53.4% for castration.

Quality of life data for Casodex showed "significant improvements" for maintenance of both sexual interest and physical capacity, AstraZeneca reported.

Quality of life was assessed at four, 12, 24 and 48 weeks through a questionnaire addressing 10 topics: pain, activity limitation, bed disability, physical capacity, overall health, sexual interest, sexual functioning, social functioning, emotional well-being and vitality.

With reference to sexual interest, bicalutamide demonstrated a significant benefit over castration. Casodex also offered an advantage over castration in the area of "physical capacity."