Abiraterone acetate significantly delayed the progression of pain and quality of life deterioration in chemotherapy-naive men with metastatic castration-resistant prostate cancer when taken in combination with prednisone.
Ethan Basch, MD
The androgen biosynthesis inhibitor abiraterone acetate (Zytiga) significantly delayed the progression of pain and quality of life deterioration in chemotherapy-naive men with metastatic castration-resistant prostate cancer (mCRPC) when taken in combination with prednisone, according to patient-reported outcomes from the COU-AA-302 trial published in Lancet Oncology.
In a median 22.2-month preplanned interim analysis, prospective data from patient-reported pain and functional status were assessed. Pain was assessed with the Brief Pain Inventory Short Form [BPI-SF] questionnaire at ≤14 days before the first treatment, day 1 of each cycle, and at treatment discontinuation. In the questionnaire, patients ranked their pain on a scale of 0—10, with lower scores representing lower levels of pain intensity.
Additionally, the study examined health-related quality of life (HRQoL) with the Functional Assessment of Cancer Therapy—Prostate (FACT-P) questionnaire on the first day of every third cycle and at treatment discontinuation. This score is calculated using three subscales and one prostate-cancer-specific scale and scores range from 0 to 156, with higher scores indicating better functional status.
"Patients with cancer experience many symptoms related to their disease and to drug side effects, but this information is generally neither measured rigorously in clinical trials nor included in US drug labels. As a result, patients often have incomplete information about how they may expect to feel with a new therapy. This study addresses this information gap towards better-informed decisions," said the lead author of the assessment, Ethan Basch, MD, in a release.
The phase III study randomized 1,088 patients with mCRPC who were asymptomatic (BPI-SF score of 0 or 1) or mildly symptomatic (BPI-SF score of 2 or 3) in a 1:1 ratio to receive abiraterone (1g daily) plus prednisone (5 mg twice daily) or placebo plus prednisone in continuous 4-week cycles. Baseline characteristics were evenly randomized between the two arms. In the abiraterone arm, baseline BPI-SF data were available for 539 patients (69% asymptomatic, 24% symptomatic, 7% symptomatic) compared to 542 for placebo (65% asymptomatic, 28% symptomatic, 8% symptomatic).
Patients receiving abiraterone plus prednisone reported a more than eight-month delay in progression of pain intensity (BPI-SF score increase of ≥30% from baseline). The median time to progression of pain intensity was 26.7 months compared to 18.4 months, for abiraterone and placebo, respectively (hazard ratio [HR] = 0.82, 95% CI, 0.67—1.00; P=0.0490). Moreover, the median time to progression of pain to the point of interfering with daily activities (BPI-SF score increase of ≥50% from baseline) was less with abiraterone (10.3 months versus 7.4 months; HR = 0.79, 95% CI, 0.67—0.93; P=0.005).
Patients who received abiraterone also reported a more than four-month delay in the median time to HRQoL deterioration compared placebo (12.7 months versus 8.3 months; HR = 0.78, 95% CI, 0.66—0.92; P=0.003). Based solely on the prostate-cancer-specific subscale of the FACT-P assessment, the median time to deterioration of HRQoL was 11.1 months compared to 5.8 months, for abiraterone and placebo, respectively (HR = 0.70, 95% CI; 0.60—0.83; P<0·0001). HRQoL deterioration was defined as a decrease of ten points from baseline in the total score and a decrease of three points from baseline in the prostate subscale.
"The majority of men with metastatic prostate cancer experience pain that is often debilitating and can have a profound impact on their ability to function, sleep, work, and their enjoyment of life. Pain is a central problem in prostate cancer and managing pain remains a major challenge," said Basch, who serves as the director of the Cancer Outcomes Research Program at the University of North Carolina Lineberger Comprehensive Cancer Center.
The FDA has indicated that validated questionnaires that assess patient-reported outcomes can function as an indicator of clinical benefit. Additionally, the ability to delay suffering represents a meaningful benefit for patients. As a result of delays in pain intensity, patients receiving abiraterone were able to delay the use of opiates and other pain medications.
"The design of this study provides a path forward for future research to utilize patient-centered endpoints," said Basch. "Not only does it provide essential information about the properties of abiraterone acetate, but it demonstrates the feasibility of rigorously measuring symptoms in a large multi-national study. It also helps identify areas of needed future methodological research.”
The FDA approved abiraterone in 2011 for use in combination with prednisone for the treatment of patients with mCRPC who had received prior chemotherapy containing docetaxel after a study showed statistically significant improvement in overall survival (OS). In 2012, the FDA extended the approval to patients with mCRPC who have not yet received chemotherapy based on results from the COU-AA-302 trial.
Basch E, Autio K, Ryan CJ, et al. Abiraterone acetate plus prednisone versus prednisone alone in chemotherapy-naive men with metastatic castration-resistant prostate cancer: patient-reported outcome results of a randomised phase 3 trial [published online ahead of print September 25, 2013]. Lancet Oncol.