Evidence Builds for Use of Zytiga in Prostate Cancer
New Agent Treats Bone Metastases and Improves Survival
This news comes from analysis of results of the Phase III COU-AA-301 trial. The study revealed that abiraterone (Zytiga) provided a highly statistically significant 3.5-month increase in overall survival (OS) in patients with mCRPC who had progressed after treatment with docetaxel. There were equally significant improvements in all of the secondary end points, such as prostate-specific antigen (PSA) response rate, time to PSA progression and progression-free survival (PFS), but the doubling of the time to SREs and the significant protection from pain progression may be at least as important from the patient’s perspective.
“Clinical benefit of abiraterone acetate in the treatment of bone metastases in patients with mCRPC crosses all dimensions. It improves pain palliation, it delays pain progression, it delays time to SRE, and the effect is sustained over all treatment cycles,”
reported Christopher J. Logothetis, MD, chair, Department of Genitourinary Medical Oncology,
, University of Texas MD Anderson Cancer Center . Presenting the pain control results from COU-AA-301 at the 2011 annual meeting of the American Society of Clinical Oncology (ASCO), Dr. Logothetis said these data confirm “meaningful improvement in symptom-free survival, in addition to the improvement in overall survival.” Houston
In this study (abstract 5420), 1,195 patients with mCRPC who had progressed after previous treatment with docetaxel and had an Eastern Cooperative Oncology Group (ECOG) status score of 2 or lower were randomized in a 2:1 ratio to 1 g of abiraterone acetate or placebo daily. Both groups received 5 mg of prednisone twice daily. Abiraterone acetate, a prodrug of abiraterone, blocks cytochrome P450 c17 (CYP17), an enzyme critical to testosterone synthesis, which, in turn, blocks androgen synthesis by the adrenal glands, testes and within the prostate tumor.
After a median follow-up of 12.8 months, OS, the primary end point, was 14.8 months in the abiraterone group and 10.8 months in the placebo group, generating a 35% relative improvement for the active therapy (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.54-0.77; P<0.001). These results were published in The New England Journal of Medicine just prior to the ASCO meeting (2011;364:1995-2005, PMID: 21612468). The PFS was 5.6 months in the abiraterone group compared with 3.6 months in the placebo group (P<0.001). PSA response rate was 29% in the abiraterone group compared with 6% in the placebo group (P<0.001). Time to PSA progression was 10.2 in the abiraterone group compared with 6.6 months in the placebo group (P<0.001).
The drug was considered even more impressive, however, when investigators dissected abiraterone’s ability to relieve the burden of symptomatic metastases, particularly bone pain. One of the most impressive results was the doubling of time to SRE, defined as pathologic fracture, spinal cord compression or palliative radiation or surgery for bone symptoms, which was a median of 301 days in the abiraterone group compared with 150 days in the placebo group. According to Dr. Logothetis, overall pain, measured in several ways, such as progression of intensity or the interference that pain imposed on daily activities, also was highly significantly less on abiraterone. Moreover, Dr. Logothetis said, actual symptomatic benefit in patients who received a full course of therapy was likely to have been even better than those reflected in this intent-to-treat analysis.
The prostate cancer expert invited to discuss the study at ASCO also emphasized the significance of these pain results, which, although preplanned, were not even formal secondary end points. Although an improvement in survival is generally required in oncology before a new treatment is considered practice-changing, the quality of life in patients with prostate cancer and bone pain deserves attention, he said.
“Not only were they palliated, they were palliated more quickly and they were palliated more fully,” said Michael J. Morris, MD, Genitourinary Oncology Service,
City. “Abiraterone and prednisone do appear to have achieved, or at least preliminarily to have achieved, the hat trick of oncology in prostate cancer. It improved how patients survived, it improved how patients feel, and it improved how patients function.” Memorial Sloan-Kettering Cancer Center, New York