BETHESDA, MarylandAstra-Zeneca failed to gain backing from the FDA’s Oncologic Drugs Advisory Committee (ODAC) for its effort to expand the indication for Casodex (150 mg bicalutamide(Drug information on bicalutamide)) in the treatment of prostate cancer. ODAC members found that the data presented were too premature to recommend that the FDA approve the company’s supplementary new drug application. They suggested, instead, that the agency delay a decision until longer-term data about the drug’s efficacy become available.
AstraZeneca is seeking approval of Casodex 150 mg as an adjuvant therapy to radical prostatectomy and radiotherapy of curative intent in patients with locally advanced nonmetastatic prostate cancer who have a high risk for disease recurrence and as immediate treatment of localized nonmetastatic prostate cancer in patients for whom therapy of curative intent is not indicated.
Casodex in a 50-mg dosage is currently approved in the United States in combination with a luteinizing hormone-releasing hormone (LHRH) analogue for the treatment of stage D2 metastatic prostate cancer. In its 150-mg form, the drug is approved for treating early-stage prostate cancer in more than 40 countries, including Canada. The availability of Casodex and its off-label use in the United States clearly weighed on the minds of ODAC members.
"This drug is going to be used because it is available; we know the drug is going to be imported from Canada," said George H. Ohye, the committee’s nonvoting industry representative. He suggested that FDA grant Casodex 150 mg accelerated approval, which would require the sponsor to conduct phase IV postmarketing trials to further confirm the drug’s safety and effectiveness.
To support its application, Astra-Zeneca presented data from three prospective, randomized, double-blind, placebo-controlled multicenter trials, known as the Early Prostate Cancer (EPC) trial program, carried out in 23 countries with a total population of 8,113 patients. The three studies are as follows:
- Trial 23, a 2-year study of 3,292 patients treated in North America, primarily in the United States: 80% received radical prostatectomy and 20% radiation therapy.
- Trial 24, a worldwide study of 3,603 patients but conducted mostly in Europe: 46% received radical prostatectomy, 19% radiation therapy, and 35% watchful waiting.
- Trial 25, which consisted of 1,218 patients enrolled in Scandinavia: 13% received radical prostatectomy, 6% radiation therapy, and 80% watchful waiting.
Both Trial 24 and 25 were extended to 5 years from the originally intended 2 years and are still in progress. The EPC studies had two major endpoints: time to progression, the choice of AstraZeneca, and survival, which the FDA preferred.
Casodex 150 mg reduced the clinical progression of prostate cancer at 3 years by 42% overall, as determined by bone scans, said William A. See, MD, professor and chief of urologic surgery, Medical College of Wisconsin, who presented efficacy data from the three trials on behalf of AstraZeneca.