Olaparib Is Linked With Decreased Pain Burden in Metastatic Castration-Resistant Prostate Cancer

Treatment with olaparib (Lynparza) resulted in decreased pain burden and better-reserved health-related quality of life (HRQOL) compared with enzalutamide (Xtandi) or abiraterone acetate (Zytiga) tablets in a select group of patients with metastatic castration-resistant prostate cancer (mCRPC).

Specifically, the PROfound study (NCT02987543) revealed that patients with mCRPC and homologous recombination repair gene alterations who had experienced disease progression following next-generation hormonal drug treatment experienced superior HRQOL and improved radiographical progression-free survival and overall survival. The findings were recently published in Lancet Oncology.

Patients receiving olaparib experienced significantly longer median time to pain compared with those receiving control (median not reached [95% CI, not reached [NR]-NR] vs 9.92 months [95% CI, 5.39-NR] which led to a hazard ratio of 0.44 (95% CI, 0.22-0.91; P = .019). Patients in the experimental arm also reported better pain interference scores compared with those in the control arm (difference in overall adjusted mean change from baseline score −0.85; 95% CI, −1.31 to −0.39; P = .0004).

Neither group reached a median time to progression of pain severity group (HR, 0.56; 95% CI 0.25-1.34]; P = .17). Among patients who had never taken opiates before the trial, the median time to first opiate use for disease-related pain was 18.0 months (95% CI, 12.8-NR) in the experimental arm and 7.5 months (3.2-NR) in the control arm (HR, 0.61; 95% CI, 0.38-0.99; P = .044).

“The PROfound study showed the clinical benefit of olaparib compared with physician’s choice of control [abiraterone or enzalutamide] in patients with metastatic castration-resistant prostate cancer with alterations in prespecified homologous recombination repair genes who had had disease progression following a previous next-generation hormonal drug,” Antoine Thiery-Vuillemin, MD, of the Department of Medical Oncology, Centre Hospitalier Universitaire Besançon, in Besançon, France, and co-investigators wrote in the study.

Investigators enrolled 245 participants with mCRPC in cohort A between February 2017 and June 4, 2019. In this cohort, all eligible participants had one of the following 15 gene alterations: BRCA1, BRCA2, or ATM and BRIP1, BARD1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, or RAD54L (cohort B), and whose disease had progressed beyond a next-generation hormonal drug.

These patients were randomized to receive either olaparib (n = 162; 66%) at 300 mg orally twice daily or a control drug (n = 83; 34%). Patients in the control arm received either enzalutamide tablets at 160 mg orally once daily or abiraterone tablets at 1000 mg orally once daily, along with 2 daily oral doses of 5 mg of prednisone. Participants were stratified by previous taxane use and measurable disease.

The median follow-up time among all groups was 6.2 months (interquartile range, 2.2-10.4) in the experimental cohort and 3.5 months (1.7-4.9) in the control cohort.

Notably, the observed meaningful improvement in FACT-P total score during treatment was superior among the olaparib group than in the control group. Nearly 10% of evaluable patients achieved a meaningful response while only 1% of their counterparts reported similarly. In addition, neither group reached the median time to first symptomatic skeletal-related event (olaparib, 95% CI, NR-NR; control group, 7.8-NR; HR, 0.37; 95% CI, 0.20-0.70; P = .0013).

“Patient-reported outcome data are important for treatment decision making for both patients and physicians, as reflected by the recommendations of the US Food and Drug Administration, European Medical Agency, and Prostate Cancer Working Group 3 to include these measures as endpoints in clinical trials for anticancer therapies,” the authors concluded. “The symptomatic and HRQOL benefits observed with olaparib compared with control treatment support the clinical benefit of improved radiographical progression-free survival in men with metastatic castration-resistant prostate cancer and homologous recombination repair gene alterations who had disease progression after a previous next-generation hormonal drug.”

Reference

Thierry-Vuillemin A, de Bono J, Hussain M, et al. Pain and health-related quality of life with olaparib versus physician's choice of next-generation hormonal drug in patients with metastatic castration-resistant prostate cancer with homologous recombination repair gene alterations (PROfound): an open-label, randomised, phase 3 trial. Lancet Oncol. 2022;1-12. doi.org/10.1016/S1470-2045(22)00017-1.