Photo Credit: Shidlovski

The following is a summary of “Olaparib for the Treatment of Patients With Metastatic Castration-Resistant Prostate Cancer and Alterations in BRCA1 and/or BRCA2 in the PROfound Trial,” published in the November 2023 issue of Oncology by Mateo, et al.

The Phase III PROfound trial aimed to assess the efficacy of olaparib monotherapy compared to abiraterone or enzalutamide (control) in metastatic castration-resistant prostate cancer (mCRPC) patients with alterations in BRCA1, BRCA2 (BRCA), and/or ATM (cohort A) who experienced disease progression on prior next-generation hormonal agent (NHA) therapy. For a study, researchers sought to present an exploratory post hoc analysis focused on the subgroup of patients with mCRPC exhibiting BRCA alterations in PROfound.

All patients in the trial had alterations in homologous recombination repair genes confirmed by tumor tissue testing, with 160 patients harboring BRCA alterations. Radiographic progression-free survival (rPFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Additionally, confirmed objective response rate and safety were assessed.

Olaparib demonstrated longer rPFS (hazard ratio [HR], 0.22 [95% CI, 0.15 to 0.32]) and OS (HR, 0.63 [95% CI, 0.42 to 0.95]) compared to the control group. Benefit in rPFS with olaparib was observed across all zygosity subgroups (biallelic [n = 88], heterozygous [n = 15], and unknown [n = 57]). Patients with BRCA2 homozygous deletions experienced prolonged responses to olaparib (n = 16; median rPFS, 16.6 months [95% CI, 9.3 to not reached]). However, some evaluations were constrained by small patient numbers. Germline DNA analysis was performed for 112 (70%) patients, showing similar risk of disease progression for patients with germline (n = 61; HR, 0.08 [95% CI, 0.03 to 0.18]) and somatic (n = 51; HR, 0.16 [95% CI, 0.07 to 0.37]) BRCA alterations.

Olaparib demonstrated improved outcomes compared to abiraterone or enzalutamide across all assessed subgroups of patients with mCRPC and BRCA alterations, indicating its efficacy in the population whose disease progressed on previous NHA therapy.

Reference: ascopubs.org/doi/10.1200/JCO.23.00339