Olaparib Reduced Pain and Yielded Better-Preserved HRQOL in Metastatic CRPC

Patients with homologous recombination repair gene–altered metastatic castration-resistant prostate cancer whose disease progressed following a previous next-generation hormonal drug experienced a reduction in pain and better-better preserved health-related quality of life with olaparib (Lynparza) vs 2 control drugs, according to findings from the phase 3 PROfound trial (NCT02987543) published in The Lancet Oncology.

In cohort A, patients in the olaparib group with BRCA1, BRCA2, or ATM gene alterations had a significantly longer median time to pain progression with a median that was not reached (NR; 95% CI, NR-NR) compared with 9.92 months (95% CI, 5.39-NR) in the control arm (HR, 0.44; 95% CI, 0.22-0.91; P = .019). In cohort B, which included patients with gene alterations in BRIP1, BARD1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, and RAD54L, the median time to pain severity progression was not reached in either group (HR, 0.56; 95% CI, 0.25-1.34; Pnominal = .17).

A total of 387 patients were enrolled on the trial and included in either cohort A (n = 245) or cohort B (n = 142). In cohort A, 162 were included in the olaparib arm and 83 were in the control arm. At data cutoff, 72 of 88 patients from both cohorts A and B had crossed over to receive olaparib after disease progression. Between both cohorts, 97 patients of 256 died in the olaparib group, and 110 deaths of 160 in both cohorts occurred more than 30 days after the final treatment dose. In the olaparib group, the median follow-up was 6.2 months vs 3.5 months in the control group.

Patients received 300 mg of olaparib tablets orally twice daily, and in the control group either enzalutamide tablets at 160 mg orally once daily or abiraterone tablets at 1000 mg orally once daily plus prednisone tablets at 5 mg orally twice daily.

The Brief Pain Inventory—Short Form (BPI-SF) compliance rate overall for the olaparib group was 90% compared with 93% in the comparator group. At baseline, the compliance rate was 96% in both arms, respectively, which decreased to 65% in the olaparib arm vs 24% in the control group 32 weeks after randomization. In patients who did not use opiates at baseline, including 113 in the olaparib group and 58 in the control group, the median time to pain progression was not reached for both groups (HR, 0.45; 95% CI, 0.20-1.06; Pnominal = .051). At 6 months, 85.2% (95% CI, 75.3%-91.3%) of patients were free of worst pain progression compared with 70.5% (95% CI, 46.9%-85.1%) in the control group. At 12 months, the estimates were 77.7% (95% CI, 64.6%-86.5%) vs 54.4% (95% CI, 27.7%-74.9%) in the olaparib and control groups, respectively.

The median time to opiate use for cancer-related pain in a subpopulation of patients who did not receive opiates at baseline was 18.0 months (95% CI, 12.8-NR) in the olaparib group and 7.5 months (95% CI, 3.2-NR) in the control group (HR, 0.61; 95% CI, 0.38-0.99; Pnominal = .044).

The Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire was completed by 97 of 162 patients in the olaparib group and 44 of 83 in the control group. The compliance rates in the olaparib arm was 68% at baseline and decreased to 57% at week 32 vs 70% and 22% in the control group, respectively. This was associated with similarity of health-related quality of life.

Ten percent of patients in the olaparib group had a clinically meaningful improvement in FACT-P score compared with 1% in the control group (OR, 8.32; 95% CI, 1.64-151.84; Pnominal = .0065).

Symptomatic skeletal-related events were reported in 15% of those in the olaparib group vs 23% in the control group. The median time to first event was NR in either group (HR, 0.37; 95% CI, 0.20-0.70; Pnominal = .0013). At 6 months and 12 months, there was a higher number of patients in the olaparib group who were free of symptomatic skeletal-related events. There were 4 patients in the olaparib group and 5 in the control group at baseline who received bisphosphonates for the prevention of symptomatic skeletal-related events.

Reference

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. Published correction appears in Lancet Oncol. 2022 Apr;23(4):e161.