Data from a third planned interim analysis of a phase III trial are consistent with earlier results supporting the efficacy and safety of abiraterone acetate (Zytiga) as a treatment for chemotherapy-naïve men with metastatic castration-resistant prostate cancer.
San Diego-Data from a third planned interim analysis of a phase III trial are consistent with earlier results supporting the efficacy and safety of abiraterone acetate (Zytiga) as a treatment for chemotherapy-naïve men with metastatic castration-resistant prostate cancer (mCRPC).
COU-AA-302 randomized 1,088 men 1:1 to treatment with abiraterone acetate, 1 gram daily plus prednisone, 5 mg twice daily or placebo daily plus prednisone, 5 mg twice daily. Eligible patients had progressive mCRPC, were asymptomatic or mildly symptomatic, and had received no prior chemotherapy. Earlier results of the randomized, double-blind trial were published in the New England Journal of Medicine (2013; 368:138-48).
The third interim analysis was performed after 55% of deaths occurred (median follow-up, 27 months), and it showed treatment benefits in both co-primary endpoints as the addition of abiraterone to prednisone reduced the risk of radiographic disease progression by 47% and of death by 21%. In addition, results from clinically meaningful secondary endpoints and exploratory quality of life outcomes showed significant differences favoring abiraterone, and the drug maintained a favorable safety profile during the relatively long period of use.
“The availability of new therapeutic opportunities makes this an exciting time for patients with mCRPC and for urologists. However, most of these agents are used in a post-chemotherapy setting, and there is still a need for effective, well-tolerated alternatives that can be used prior to chemotherapy or in men for whom chemotherapy is not an option,” said first author Fred Saad, MD, who presented the current findings at the AUA annual meeting in San Diego.
“I believe abiraterone acetate is a safe, effective, and well-tolerated hormonal therapy that will allow interested urologists the opportunity to be directly involved in the management of patients with mCRPC,” said Dr. Saad, professor of surgery at the University of Montreal and chief of urology and director of urologic oncology at the University of Montreal Hospital Centre.
The two phase III study groups were well matched at baseline. Median time from initial diagnosis was about 5 years, about 80% of men had bone metastases, about 50% had measurable soft tissue disease, and about one-third were on bone-targeted therapy. At the time of the interim analysis, 77% of abiraterone patients and 89% of controls had discontinued therapy, mostly because of disease progression.
“Less than 10% of patients had stopped treatment because of adverse events,” Dr. Saad said.
Radiographic progression was centrally analyzed using a standardized definition. In the third interim analysis, abiraterone doubled the time to radiographic progression-free survival compared with placebo, from 8.3 to 16.5 months.
“It was reassuring that regardless of entry PSA, patient age, or region, every subgroup analyzed benefited from abiraterone,” Dr. Saad said.
Abiraterone improved median overall survival versus control from 30.1 to 35.3 months. The difference between groups only trended toward statistical significance, perhaps because most patients who discontinued study treatment went on to subsequent therapy, which included abiraterone in 16% of controls, Dr. Saad said.
Secondary endpoint analyses showed abiraterone significantly prolonged time to opiate use and time to chemotherapy initiation, as well as significantly improved time to ECOG performance status deterioration and time to PSA progression. The exploratory quality of life analyses looking at Brief Pain Inventory-Short Form and Functional Assessment of Cancer Therapy-Prostate scores also showed significant treatment benefits.
Findings from an ongoing analysis showed addition of bone-targeted therapy did not affect either of the co-primary endpoints, but it did appear to augment improvements in symptom progression.
Safety analyses showed abiraterone was well tolerated. Grade 3/4 toxicities for all adverse events occurred at rates of <10% in the abiraterone group. Rates of grade 3/4 liver enzyme elevations were higher with abiraterone, but they occurred in the first 3 months of treatment and were always reversible.
Dr. Saad is a paid consultant to and receives research funding from Janssen. Several of Dr. Saad’s co-authors are consultants/advisers and/or investigators, meeting participants/lecturers, and/or employees of Janssen.UT