Kurt Miller, MD, PhD
Treatment with abiraterone acetate (Zytiga) plus prednisone demonstrated an 11.8-month improvement in overall survival (OS) compared with prednisone and placebo for men with less advanced, chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC), according to a post-hoc analysis of the phase III COU-AA-302 trial presented at the 2016 European Association of Urology Congress.
Median OS with abiraterone was 53.6 months compared with 41.8 months with placebo for men with a PSA below 80 ng/ml, Gleason score below 8, and a brief pain inventory (BPI) score of 0 to 1. This improvement in OS was equivalent to a 39% reduction in the risk of death (HR, 0.61; 95% CI, 0.43-0.87; P
= .0055). Across the full study, abiraterone demonstrated a 4.4-month improvement in OS versus placebo (HR, 0.81; 95% CI, 0.70-0.93; P
“Post-hoc analyses, such as this, are very important in helping us to identify the patients who could benefit most from therapies, such as novel hormone agents, and at what stage of a patient’s disease they could be most effective,” lead investigator Kurt Miller, MD, PhD, Department of Urology, Chariteì Berlin, Berlin, Germany, said in a statement.
The FDA approved abiraterone as a treatment for chemotherapy-naive men with mCRPC in December 2012. The approval was based on improvement in median radiographic progression-free survival (rPFS), time-to-opiate use, and time-to-cytotoxic chemotherapy. In March 2015, the label was updated to add mature OS data.
In the COU-AA-302 trial, 1088 patients were randomized in a 1:1 ratio to abiraterone plus prednisone (n = 546) or prednisone and placebo (n = 542). Abiraterone was administered at 1000 milligram once daily and prednisone was administered at 5 mg twice daily.
The post-hoc analysis looked specifically at men with less advanced mCRPC or those with more aggressive disease, specifically patients with a BPI of ≥2 and/or PSA of ≥80 ng/ml and/or a Gleason score of ≥8. In addition to OS, the post-hoc analysis explored time to chemotherapy, time to opiate use, and median time on treatment.
For those with less aggressive cancer, the median time to chemotherapy was 37.0 months with abiraterone compared with 24.3 months with placebo (HR, 0.64; 95% CI, 0.46-0.89; P
= .0073). Additionally, time to opiate use was delayed by 31% for men in the abiraterone arm (median not reached vs 41.0 months; HR, 0.69; 95% CI, 0.48-0.99; P
= .0409). Median time on treatment was 20.4 versus 11.2 months with abiraterone and placebo, respectively (HR, 0.41; 95% CI, 0.31-0.54; P
In men with more aggressive disease, the median OS was improved by 2.8 months with abiraterone (HR, 0.84; 95% CI, 0.72-0.99; P
= .0321). For abiraterone and placebo, respectively, the median time to chemotherapy was 23.3 versus 14.5 months (HR, 0.71; 95% CI, 0.60-0.85; P
= .0001) and median time to opiate use was 30.5 versus 19.3 months (HR, 0.70; 95% CI, 0.59-0.84; P
= 0.0001). Median time on treatment was 12.3 months with abiraterone versus 7.2 months with placebo (HR, 0.54; 95% CI, 0.46-0.62; P
“As men with prostate cancer are living longer, quality of life is an increasingly important factor for them and their families,” said Miller. “It is therefore encouraging to see that when used earlier, patients can stay on Zytiga for longer and delay the need for additional, more invasive treatments.”
Across the full study at the final 49.2-month analysis, the median OS was 34.7 months with abiraterone versus 30.3 months with placebo (HR, 0.81; 95% CI, 0.70-0.93; P
= .0033). Median rPFS was 16.5 versus 8.3 months, for abiraterone and placebo, respectively (HR, 0.53; 95% CI, 0.45-0.62; P
At the time of the final analysis, 92% of patients in the abiraterone acetate arm and 100% in the placebo arm discontinued therapy. Disease progression was the primary cause of discontinuation in both arms. The most common grade 3/4 adverse events associated with abiraterone versus placebo were cardiac disorders (8% vs 4%), increased alanine aminotransferase (6% vs <1%], and hypertension (5% vs 3%).
“We hope that this additional analysis will help healthcare professionals to define the most effective treatment pathway for individual patients,” Jane Griffiths, Company Group Chairman, Janssen Europe, the Middle East and Africa (EMEA), said in a statement. “We remain committed to continuing our research in this area with the aim of helping to improve outcomes for men affected by this disease now and in the future.”
The FDA initially approved abiraterone in 2011 as a treatment for men with mCRPC following prior docetaxel, based on a 4.6-month extension in OS seen with the androgen synthesis inhibitor. In this trial, which was labeled COU-AA-301, the median OS was 15.8 months with abiraterone compared with 11.2 months with placebo (HR, 0.740; 95% CI, 0.638-0.859).
Miller K, et al. The phase 3 COU-AA-302 study of abiraterone acetate (AA) in men with chemotherapy (CT)-naïve metastatic castration-resistant prostate cancer (mCRPC): Stratified analysis based on pain, prostate-specific antigen (PSA) and Gleason score (GS). Presented at: European Association of Urology 2016 Congress; March 11-15, 2016; Munich, Germany. Poster 61.