Abiraterone Acetate Improves Survival in Prostate Cancer Patients

Chicago—A phase 3 study found that patients taking abiraterone acetate had a median increase in survival of 4.5 months compared with placebo and that the level of circulating tumor cells (CTCs) correlated with survival. Howard Scher, MD, the study’s lead author, discussed the results in an oral abstract session at the ASCO meeting. The US Food and Drug Administration approved abiraterone acetate in April in combination with prednisone to treat men with metastatic castration-resistant prostate cancer (mCRPC) that had progressed after receiving a docetaxel-containing chemotherapy regimen. Abiraterone acetate is a CYP17 inhibitor that blocks androgen synthesis in the testes, adrenals, and the tumor. The approval was based on an interim analysis of a phase 3 trial, which found that after 552 deaths had occurred, patients taking abiraterone acetate had a median increase in survival of 3.9 months. The double-blind, placebo-controlled trial (COU-AA-301) included 1195 patients with mCRPC who were randomized in a 2:1 ratio to receive 1 mg of abiraterone acetate once daily and 5 mg of prednisone twice daily or placebo and prednisone, according to Dr. Scher. In the updated analysis presented at the ASCO meeting that included 775 deaths, the abiraterone acetate group had a median overall survival of 15.8 months compared with 11.2 months for the placebo group (hazard ratio, 0.74; 95% confidence interval, 0.638-0.859; P<.0001). The median follow-up was 20.2 months. Dr. Scher said that the findings revealed that CRPCs are not uniformly hormone refractory. Dr. Scher said researchers were also interested in understanding if there was a biomarker panel that could be used to understand the survival benefit associated with abiraterone acetate and potentially serve as a surrogate end point. Currently, only 1 CTC assay (the CellSearch® CTC test) is approved for breast, colorectal, and prostate cancer. The test is reported as the number of cells per 7.5 mL of blood, with <5 CTCs classified as favorable and ≥5 CTCs classified as unfavorable. In phase 2 trials involving abiraterone acetate, there was a high CTC conversion rate from unfavorable to favorable in the postchemotherapy CRPC-treated population, which was the same population studied in the phase 3 trial. In one of the phase 2 trials, 51% of patients had a ≥50% prostate-specific antigen (PSA) decline, while the other phase 2 trial showed that 43% of patients had a ≥50% PSA decline. In addition, the phase 2 trials revealed that 41% and 34% of patients with an unfavorable CTC count had a favorable CTC count after treatment. Based on the phase 2 results, the authors of the COU-AA-301 study included CTC enumeration as a tertiary end point with the long-term objective of accelerating drug approvals. Dr. Scher said this was the first phase 3 trial to assess CTC enumeration as an efficacy response biomarker or surrogate for overall survival in a regulatory context. He added that the study was not designed to address the use of CTCs for managing individual patients. The authors examined the CTC counts of 972 patients at baseline and then every 4 weeks. At each interval (weeks 4, 8, and 12), there was a significantly higher proportion of patients who converted from unfavorable to favorable CTC counts in the abiraterone acetate group compared with the placebo group (P<.0001 in each scenario). Dr. Scher added that baseline CTC and lactate dehydrogenase (LDH) were prognostic for overall survival, while PSA was not prognostic. In addition, the initial biomarker panel with CTC and LDH was strongly associated with survival. After adjusting for the biomarker panel, there was no treatment effect on survival, according to Dr. Scher.