As reported in The Lancet Oncology by Fred Saad, MD, FRCS, and colleagues, an analysis of a phase II trial found no significant differences in health-related quality of life or pain measures with the addition of olaparib to abiraterone in patients with metastatic castration-resistant prostate cancer.
The double-blind trial included 142 patients from sites in 11 countries in Europe and North America who had received docetaxel and up to one additional line of previous chemotherapy. They were randomly assigned between November 2014 and July 2015 to receive oral olaparib at 300 mg (n = 71) or placebo (n = 71) twice daily combined with oral abiraterone at 1,000 mg once daily and oral prednisone or prednisolone at 5 mg twice daily. The trial showed that the addition of olaparib to abiraterone significantly prolonged progression-free survival. The patient-reported outcome analysis was a prespecified exploratory analysis.
Prespecified outcomes were:
- Change from baseline in Brief Pain Inventory-Short Form (BPI-SF) worst pain, single-item worst bone pain, and Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Outcome Index (TOI) scale scores
- Time to deterioration in BPI-SF worst pain and single-item worst bone pain
- Analysis of the EuroQol-5 five-dimension five level (EQ-5D-5L) pain and discomfort domain.
The analysis population consisted of all randomly assigned patients.
Key Findings
Median follow-up was 15.9 months (interquartile range [IQR] = 8.1–25.5 months) in the olaparib group and 24.5 months (IQR = 8.1–27.6 months) in the control group. Overall, least-squares mean changes from baseline in BPI-SF worst pain, single-item worst bone pain, and FACT-P TOI remained stable across all visits for patients in both treatment groups. Adjusted mean change in FACT-P TOI (scale range = 0–104; 5-point difference defined as clinically meaningful) from baseline across all visits was −0.10 (95% CI = −2.50 to 2.71) in the olaparib group vs −1.20 (95% CI = −4.15 to 1.74) in the control group (difference = 1.30, 95% CI = −2.70 to 5.30, P = .52).
Time to deterioration in pain was similar in both groups. Hazard ratios for the olaparib vs control group were 0.90 (95% confidence interval [CI] = 0.62–1.32, P = .30) for BPI-SF worst pain and 0.85 (95% CI = 0.59–1.22, P = .18) for single-item worst bone pain. Similar improvements in the pain and discomfort domain of the EQ-5D-5L were observed in both groups through week 48, after which more patients in the olaparib vs control group reported improvement.
The investigators concluded, “In these prespecified exploratory analyses, there was no significant difference in pain or health-related quality of life when olaparib was added to abiraterone. In this phase II trial, a statistically significant radiographic progression-free survival benefit was observed with the olaparib plus abiraterone combination. These results suggest that the improved survival benefits observed when combining olaparib with abiraterone does not result in different health-related quality of life compared with placebo plus abiraterone. Phase III studies are required to validate these results.”
Dr. Saad, of Centre Hospitalier de l’Université de Montréal, is the corresponding author for The Lancet Oncology article.
Disclosure: This study was funded by AstraZeneca and is part of an alliance between AstraZeneca and Merck Sharp & Dohme. For full disclosures of the study authors, visit thelancet.com.
