An interim analysis of the COU-AA-302 phase III trial in asymptomatic or mildly symptomatic chemotherapy-naive men with metastatic castration-resistant prostate cancer showed that the addition of abiraterone (Zytiga) to prednisone significantly delayed radiographic progression and improved overall survival although the prespecified significance level of P ≤ .0008 was not reached.1 On this interim analysis, the addition of abiraterone also significantly delayed time to opiate use for cancer-related pain, patient-reported pain intensity progression, and health-related quality-of-life deterioration.
In a recently reported analysis in The Lancet Oncology, Ethan Basch, MD, of The University of North Carolina at Chapel Hill, and colleagues described patient-reported outcomes in the second preplanned interim analysis of the trial. The analysis showed that the addition of abiraterone delayed patient-reported pain progression and health-related quality-of-life deterioration compared with prednisone alone.
Study Details
In the multinational, double-blind trial, 1,088 patients with progressive, metastatic castration-resistant prostate cancer were randomly assigned to receive abiraterone at 1 g/d plus prednisone (5 mg twice daily; n = 546) or prednisone plus placebo (n = 542) in continuous 4-week cycles. Eligible patients were asymptomatic (score of 0 or 1 on item three of the Brief Pain Inventory Short Form [BPI-SF] questionnaire) or mildly symptomatic (score of 2 or 3) and had not previously received chemotherapy.
Pain was assessed with the BPI-SF questionnaire, and health-related quality of life was assessed with the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire. Predefined thresholds for pain progression and deterioration in functional status were: increases of ≥ 30% from baseline for the progression of mean pain intensity and progression of worst pain intensity items and an increase of ≥ 50% of baseline standard deviation for the progression of interference of pain with activities of daily living item on the BPI-SF; and decreases of 10, 9, 9, 3, and 3 points from baseline for the total score, general function score (physical well-being, social and family well-being, emotional well-being, and functional well-being subscales), trial outcome index, prostate cancer–specific subscale, and general function subscales, respectively, on FACT-P. No adjustments for multiple comparisons were made because of the exploratory nature of these analyses.
At baseline the abiraterone/prednisone and prednisone groups had similar FACT-P and subscale scores, 69% vs 65% were asymptomatic and 24% vs 28% were mildly symptomatic, and 65% vs 69% were using no analgesics and 32% vs 26% were using nonopiate analgesics. In both groups, cumulative compliance for completion of both the BPI-SF and FACT-P was ≥ 95% for all treatment cycles.
Pain Progression
At the time of the second prespecified interim analysis, median follow-up was 22.2 months (interquartile range, 20.2–24.8 months). The abiraterone/prednisone group had significantly prolonged median time to progression of mean pain intensity (26.7 vs 18.4 months, hazard ratio [HR] = 0.82, P = .0490) and median time to progression of pain interference with daily activities (10.3 vs 7.4 months, HR = 0.79, P = .005). The abiraterone/prednisone group had a nonsignificantly increased median time to progression of worst pain intensity (26.7 vs 19.4 months, HR = 0.85, P = .109.
In a post hoc sensitivity analysis in which progression was defined as change in BPI-SF worst pain intensity by two points from baseline, median time to progression was not reached in either group; median time to progression at the 25th percentile was significantly longer with abiraterone/prednisone (14.8 vs 12.0 months, HR = 0.78, P = .045).
Health-Related Quality-of-Life Deterioration
On FACT-P assessment, abiraterone/prednisone was associated with significantly prolonged median time to health-related quality-of-life deterioration on FACT-P total score (12.7 vs 8.3 months, HR = 0.78, P = .0028), prostate cancer–specific subscale (11.1 vs 5.8 months, HR = 0.70, P < .0001), trial outcome index (13.9 vs 9.3 months, HR = 0.75, P = .0006), general function score (16.6 vs 11.1 months, HR = 0.76, P = .0023), emotional well-being subscale (22.1 vs 14.2 months, HR = 0.71, P = .0008), and functional well-being subscale (13.3 vs 8.4 months, HR = 0.76, P = .0012), with no difference between groups being observed only for the social and family well-being subscale (18.4 vs 16.6 months, HR = 0.94, P = .5283).
The investigators concluded: “Abiraterone plus prednisone delays patient-reported pain progression and [health-related quality-of-life] deterioration in chemotherapy-naive patients with metastatic castration-resistant prostate cancer. These results provide further support for the efficacy of abiraterone in this population.” ■
Disclosure: The study was funded by Janssen Research & Development. For full disclosures of the study authors, visit www.thelancet.com.
References
1. Ryan CJ, Smith MR, de Bono JS, et al: Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 368:138-148, 2013.
2. 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. Lancet Oncol 14:1193-1199, 2013.
