July 2023: The Food and Drug Administration (FDA) approved olaparib (Lynparza, AstraZeneca Pharmaceuticals LP) with abiraterone and prednisone (or prednisolone) for adults with deleterious or suspected deleterious BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer (mCRPC), as determined by an FDA-approved companion diagnostic test.
The effectiveness was tested in the PROpel study (NCT03732820), which had 796 people with mCRPC sign up. Patients were given either olaparib with abiraterone or a dummy with abiraterone. They were also given either prednisone or prednisolone. Patients had to get an orchiectomy first, and if that didn’t happen, they were given gonadotropin-releasing hormone (GnRH) analogues. Patients who had received systemic treatment for mCRPC before were not eligible, but those who had received docetaxel before for advanced hormone-sensitive prostate cancer were. Randomization was based on where the tumours were and if docetaxel had been used before. Foundation Medicine, Inc. used the FoundationOne CDx and FoundationOne Liquid CDx tests to look for BRCA mutations in all of the clinical samples that were available.
Investigator-assessed radiological progression-free survival (rPFS) based on RECIST version 1.1 for soft tissue lesions and Prostate Cancer Working Group standards for bone lesions was the most important measure of effectiveness. A second objective was overall survival (OS).
In the ITT group, there was a statistically significant difference between olaparib with abiraterone and placebo with abiraterone in terms of rPFS. An exploratory subgroup study of 85 patients with BRCAm (11% of the ITT population) showed that the median rPFS was not reached in the olaparib with abiraterone arm, while it was 8 months (95% CI: 6–15) in the placebo with abiraterone arm (hazard ratio [HR]: 0.24 [95% CI: 0.12–0.45]). With these patients, the OS HR was 0.30 (95% CI: 0.15–0.59). In the 711 patients (89% of the ITT population) without BRCAm, the rPFS HR was 0.77 (95% CI: 0.63, 0.96) and the OS HR was 0.92 (95% CI: 0.74, 1.14), which suggests that patients with BRCAm were mostly responsible for the improvement in rPFS seen in the ITT population.
Patients who took olaparib plus abiraterone had anaemia 48% of the time, fatigue 38% of the time, nausea 30% of the time, diarrhoea 19% of the time, reduced appetite 16% of the time, lymphopenia 14% of the time, dizziness 14% of the time, and abdominal pain 13% of the time. 72 people (18%) needed at least one blood transfer, and 46 people (12%) needed more than one.
The suggested amount of olaparib is 300 mg, which should be taken by mouth twice a day, with or without food. The suggested dose of abiraterone is 1000 mg, which should be taken by mouth once a day. Abiraterone should be given with 5 mg of prednisone or 5 mg of prednisolone twice a day. Patients should also get a GnRH analogue at the same time or have had a bilateral orchiectomy in the past.