Treatment with olaparib was associated with a reduction in pain and improvement in health-related quality of life (HRQOL) compared with physician’s choice of hormone therapy in patients with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) gene alterations, according to results of the phase 3 PROfound trial published in The Lancet Oncology.1

Earlier data from the PROfound trial (ClinicalTrials.gov Identifier: NCT02987543) showed significantly improved radiographical progression-free survival (rPFS) and overall survival with olaparib compared with physician’s choice control treatment (enzalutamide or abiraterone) in patients with mCRPC and HRR alterations whose disease had progressed after at least 1 previous next-generation hormone therapy.2

In a follow-up analysis, researchers evaluated pain and HRQOL measures in these patients.1 The study enrolled 245 patients with at least 1 alteration in BRCA1, BRCA2, or ATM. Of these, 162 patients received olaparib and 83 patients received control treatment (enzalutamide or abiraterone plus prednisone). Pain and HRQOL were assessed using the Brief Pain Inventory-Short Form and the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaires, respectively.


Continue Reading

At the data cutoff (June 4, 2019), the median follow-up was 6.2 months in the olaparib arm and 3.5 months in the control arm.

There was a significantly longer median time to pain progression in the olaparib arm than in the control arm. The median was not reached and 9.92 months, respectively (hazard ratio [HR], 0.44; 95% CI, 0.22-0.91; P =.019).

In a subset of patients who had not used opiates at baseline (113 in the olaparib arm and 58 in the control arm), the median time to first opiate use for cancer-related pain was significantly longer in the olaparib arm than in the control arm — 18.0 months and 7.5 months, respectively (HR, 0.61; 95% CI, 0.38-0.99; P =.044).

The median time to progression of pain severity was not reached in either treatment arm (HR, 0.56; 95% CI, 0.25-1.34; P =.17), and the median time to first symptomatic skeletal-related event was not reached in either arm (HR, 0.37; 95% CI, 0.20-0.70; P =.0013).

There was a clinically meaningful improvement in the FACT-P total score for 10% of patients in the olaparib arm and 1% in the control arm (odds ratio, 8.32; 95% CI, 1.64-151.84; P =.0065).

“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,” the researchers concluded.

Disclosure: This research was supported by AstraZeneca and Merck Sharp & Dohme. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

  1. Thiery-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;23(3):393-405. doi:10.1016/S1470-2045(22)00017-1
  2. de Bono J, Mateo J, Fizazi K, et al. Olaparib for metastatic castration-resistant prostate cancer. N Engl J Med. 2020;382(22):2091-2102. doi:10.1056/NEJMoa1911440