FDA Approves Abiraterone, a Corticosteroid and Olaparib for BRCA-Mutated Prostate Cancer

BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer patients gained an FDA-approved treatment option on 31 May 2023: olaparib (Lynparza, AstraZeneca) in combination with abiraterone and prednisone (or prednisolone). The FDA is the Food and Drug Administration of the United States. Eligibility for this treatment should be established using a BRCA mutation-detecting genetic test. This approval also highlights the importance of routine genetic testing in advanced prostate cancer.

Scientific advances in medicine can make an important difference to patients’ lives. These advances often take the form of approval for a new drug or treatment. FDA approval documents the safety and efficacy of these new medicines and treatments. Today we share an example: FDA approval of olaparib, abiraterone and prednisone (or prednisolone) for BRCA-mutated metastatic castration-resistant prostate cancer.

An Overview of Treatment for Metastatic Castration-Resistant Prostate Cancer

Metastatic castration-resistant prostate cancer (mCRPC) is an advanced stage of prostate cancer. The cancer has spread to other parts of the body, usually the bones and lymph nodes (metastasized ). In addition, “castration-resistant” means that the cancer no longer responds to standard hormone treatments (androgen deprivation therapy, or ADT). These treatments generally aim to lower male hormones (androgens), because they support prostate cancer-cell growth.

The rate at which prostate cancer progresses to mCRPC varies between patients and generally depends on cancer stage, aggressiveness and treatment response. Some early-stage, low-grade cancers grow slowly and require lifelong monitoring, and most of these patients do not progress to mCRPC. More aggressive or advanced prostate cancers are more likely to progress to mCRPC, particularly if they do not respond to treatment. Nevertheless, approximately 10-20% of men with prostate cancer eventually reach the mCRPC stage. Finding effective treatment options for these patients is therefore extremely important.

Androgen deprivation therapy (ADT) is generally used for mCRPC, often alongside other treatments. Put simply, it aims to reduce male hormones (androgens) in the body, because they support prostate cancer-cell growth. This approach is recommended for most people with prostate cancer in particular.

Because the disease is advanced, newer drugs such as abiraterone, apalutamide, docetaxel or enzalutamide are generally added to ADT in these patients.

FDA Approval Based on the PROpel Study

In PROpel, 796 patients with mCRPC were randomized (assigned at random to one of two groups) to olaparib plus abiraterone or abiraterone plus placebo, and also received prednisone or prednisolone. Patients had to have undergone orchiectomy previously or, if not, were receiving gonadotropin-releasing hormone (GnRH) analogs. Orchiectomy means complete surgical removal of the testicles.

Patients who had previously received systemic treatment for mCRPC were excluded, although prior docetaxel for metastatic hormone-sensitive prostate cancer was allowed. Randomization was stratified by metastatic site and prior docetaxel use. All available clinical samples were retrospectively tested for BRCA mutation status using FoundationOne CDx and FoundationOne Liquid CDx (Foundation Medicine, Inc.).

Results

Olaparib plus abiraterone showed significant superiority over placebo plus abiraterone in radiological progression-free survival (rPFS) outcomes.

In the 11% of the entire group with BRCAm, comprising 85 patients, median rPFS could not be determined in the olaparib plus abiraterone group, compared with 8 months in those receiving placebo plus abiraterone (95% CI: 6, 15). Adding olaparib reduced mortality risk by 70% in these patients (hazard ratio for overall survival 0.30; 95% CI: 0.15, 0.59).

In the 89% of the entire group without BRCAm , comprising 711 patients, adding olaparib reduced progression risk by 23% and mortality risk by 8%.

These findings show that the progression-free survival improvement observed in the entire group was mainly driven by patients with BRCAm mutations.

In patients receiving olaparib plus abiraterone, the most common (10% or more) side effects were anemia (48%), fatigue (38%), nausea (30%), diarrhea (19%), decreased appetite (16%), lymphopenia (14%), dizziness (14%) and abdominal pain (13%). Seventy-two patients (18%) needed at least one blood transfusion, and 46 (12%) required more than one.

The recommended olaparib dose is 300 mg orally twice daily, with or without food. The recommended abiraterone dose is 1000 mg orally once daily. Prednisone or prednisolone 5 mg should be taken orally twice daily alongside abiraterone. Patients should also receive a concurrent GnRH analog or have previously undergone bilateral orchiectomy.

This approval represents important progress in treating BRCA-mutated metastatic castration-resistant prostate cancer. The results demonstrate the effectiveness of the new combination, particularly in patients with BRCA mutations. However, like any drugs, olaparib, abiraterone and prednisone have side effects, and doctors should assess the most suitable treatment options for each patient. This development affects patients’ lives and offers new hope in the fight against cancer. We believe such scientific advances play a critical role in developing more effective approaches to cancer.

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