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Pain and Quality of Life in the PROfound Trial: Olaparib vs Next-Generation Hormonal Agent in Metastatic Castration-Resistant Prostate Cancer With HRR Gene Alterations


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In an analysis from the phase III PROfound trial reported in The Lancet Oncology, Thiery-Vuillemin et al found that olaparib was associated with better pain outcomes and preservation of health-related quality of life (QOL) vs enzalutamide or abiraterone plus prednisone in a cohort of men with metastatic castration-resistant prostate cancer with homologous recombination repair (HRR) gene alterations. The trial showed significant improvement in radiographic progression–free and overall survival with olaparib and supported the May 2020 approval of the agent in this setting.

Study Details

The open-label trial included 387 patients with alterations in any of 15 HRR genes and disease progression on a previous next-generation hormonal drug. They were randomly assigned 2:1 to receive olaparib at 300 mg twice daily (n = 256) or physician’s choice (n = 131) of enzalutamide at 160 mg once daily or abiraterone at 1,000 mg once daily plus prednisone at 5 mg twice daily. Treatment continued until disease progression or unacceptable toxicity.

The current prespecified analysis assessed pain, QOL, symptomatic skeletal-related events, and time to first opiate use for cancer-related pain in cohort A, which included 245 patients with alterations in BRCA1, BRCA2, or ATM; of these, 162 received olaparib and 83 received control treatment. Pain was assessed with the Brief Pain Inventory–Short Form, and QOL was assessed with the Functional Assessment of Cancer Therapy–Prostate (FACT-P).

Key Findings

Median time to pain progression was not reached (95% confidence interval [CI] = not reached–not reached] in the olaparib group vs 9.92 months (95% CI = 5.39 months–not reached) in the control group (hazard ratio [HR] = 0.44, 95% CI = 0.22–0.91, P = .019). Pain interference scores were significantly better in the olaparib group (difference in overall adjusted mean change from baseline score = −0.85, 95% CI = −1.31 to −0.39, nominal P = .0004).

Median time to progression of pain severity was not reached in either group (95% CI = not reached–not reached for both groups, HR = 0.56, 95% CI = 0.25–1.34, nominal P = .17). Rates of no pain severity progression were 87.8% vs 77.4% at 6 months and 81.7% vs 61.9% at 12 months. Among 113 patients in the olaparib group and 58 in the control group who did not use opiates for pain at baseline, median time to first opiate use for cancer-related pain was 18.0 months (95% CI = 12.8 months–not reached) in the olaparib group vs 7.5 months (95% CI = 3.2 months–not reached) in the control group (HR = 0.61, 95% CI = 0.38–0.99, nominal P = .044).

Analysis of FACT-P total scores suggested that QOL was similar between treatment groups at baseline and consistently higher for the olaparib group for the duration of treatment. Clinically meaningful improvement in FACT-P total score during treatment was observed in 15 (10%) of 152 evaluable patients in the olaparib group vs 1 (1%) of 77 evaluable patients in the control group (odds ratio = 8.32, 95% CI = 1.64–151.84, nominal P = .0065).

Median time to first symptomatic skeletal-related event was not reached in the olaparib group (95% CI = not reached–not reached) vs not reached (95% CI = 7.8 months–not reached) in the control group (HR = 0.37, 95% CI = 0.20–0.70, nominal P = .0013). Proportions of patients remaining free of symptomatic skeletal-related events were 89.5% vs 77.1% at 6 months and 77.6% vs 53.6% at 12 months.

The investigators concluded, “Olaparib was associated with reduced pain burden and better-preserved health-related QOL compared with the two control drugs in men with metastatic castration-resistant prostate cancer and HRR gene alterations who had disease progression after a previous next-generation hormonal drug. Our findings support the clinical benefit of improved radiographical progression–free survival and overall survival identified in PROfound.”

Antoine Thiery-Vuillemin, MD, of the Department of Medical Oncology, Centre Hospitalier Universitaire Besançon, France, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by AstraZeneca and Merck Sharp & Dohme. For full disclosures of the study authors, visit thelancet.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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