medwireNews: Olaparib use is associated with reduced pain burden and better preservation of health-related quality of life (HRQoL) relative to control treatments in men with metastatic castration-resistant prostate cancer (mCRPC) harboring BRCA1, BRCA2, or ATM alterations, research shows.
The phase 3 PROfound trial, carried out in men who had disease progression after a previous next-generation hormonal drug, also revealed that olaparib use was associated with delays in the time to first opiate use and first symptomatic skeletal-related event, report Antoine Thiery-Vuillemin (Universitaire Besançon, France) and co-authors in The Lancet Oncology.
They say their “findings support the clinical benefit of improved radiographical progression-free survival and overall survival identified in PROfound,” as previously reported by medwireNews.
The study included 245 men with mCRPC carrying mutations in the homologous recombination repair (HRR) genes BRCA1, BRCA2, and ATM who were randomly assigned to receive olaparib 300 mg twice daily (n=162) or a physician’s choice of either enzalutamide 160 mg/day or abiraterone 1000 mg/day plus prednisone 5 mg twice daily (n=83).
The current analysis of pain and HRQoL outcomes revealed that the median time to pain progression, measured using the Brief Pain Inventory-Short Form, was not reached in the olaparib group but was 9.9 months in the control group, a significant difference with a hazard ratio (HR) of 0.44.
Pain interference scores also significantly differed between the two groups, with the adjusted least-square means change from baseline 0.85 points lower in the olaparib versus control arms, indicating less pain interference with olaparib than with control. And the researchers note that “[t]his benefit was present across the seven pain interference subscales.”
The team found that the median time to pain severity progression was not reached in either group, but 12 months after randomization, 81.7% of participants receiving olaparib and 61.9% of those given enzalutamide or abiraterone remained free from pain severity progression.
For the final pain-related outcome, Thiery-Vuillemin et al found that the median time to first opiate use for cancer-related pain was significantly longer in the olaparib group than in the control group, at 18.0 versus 7.5 months (HR=0.61) among the 113 and 58 patients, respectively, who were opiate-naïve at baseline.
Using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) total score, the investigators observed that individuals who received olaparib were a significant 8.3 times more likely to experience a clinically meaningful improvement in HRQoL than those treated with enzalutamide or abiraterone, at rates of 9.9% versus 1.3%.
They were also more likely to be free from symptomatic skeletal-related events at 12 months (77.6 vs 53.6%), but the median time to a first symptomatic skeletal-related event was not reached for either treatment group.
Of note, Thiery-Vuillemin and colleagues observed similar symptomatic and HRQoL benefits with olaparib when they analyzed data for the full PROfound study population, which included men with an additional 12 HRR gene alterations.
The authors conclude: “HRQOL is an important consideration in patients with metastatic castration-resistant prostate cancer and these analyses have shown that compared with the two control drugs, olaparib was associated with better control of disease symptoms, via reduction in the burden of pain, and better-preserved HRQOL.”
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Lancet Oncol 2022; doi:10.1016/S1470-2045(22)00017-1