The FDA has granted approval to FoundationOne CDx and FoundationOne Liquid CDx as companion diagnostics for olaparib (Lynparza) in combination with abiraterone and prednisone or prednisolone, marking a significant advancement in the treatment of adults with deleterious or suspected deleterious BRCA-mutated metastatic castration-resistant prostate cancer (mCRPC). This approval, announced by Foundation Medicine, follows the FDA's 2023 approval of olaparib in combination with abiraterone and prednisone or prednisolone for the same patient population, based on the phase 3 PROpel trial results.
The companion diagnostics are designed to identify patients who are most likely to benefit from the olaparib combination therapy. FoundationOne CDx analyzes tissue samples, while FoundationOne Liquid CDx utilizes liquid biopsies, providing flexibility in accessing genomic information. Both tests analyze over 300 cancer-related genes to provide comprehensive genomic insights.
Clinical Evidence from the PROpel Trial
The approval is underpinned by data from the phase 3 PROpel trial (NCT03732820), which evaluated the efficacy and safety of olaparib in combination with abiraterone and prednisone or prednisolone in patients with mCRPC. The primary endpoint of the trial was investigator-assessed radiological progression-free survival (rPFS).
An exploratory subgroup analysis of patients with BRCA mutations (11% of the intent-to-treat population) showed a significant improvement in rPFS. The median rPFS was not reached in the olaparib arm compared to 8 months (95% CI, 6-15) for patients receiving placebo with abiraterone (HR, 0.24; 95% CI: 0.12-0.45). In patients without BRCA mutations (89% of the intent-to-treat population), the rPFS hazard ratio was 0.77 (95% CI, 0.63-0.96).
Overall survival (OS), a key secondary endpoint, also favored the olaparib arm in patients with BRCA mutations, with a hazard ratio of 0.30 (95% CI, 0.15-0.59). In patients without BRCA mutations, the hazard ratio was 0.92 (95% CI, 0.74-1.14).
Expert Commentary
"This approval reinforces the importance of testing for genomic mutations at metastatic diagnosis to help guide treatment decisions," said Mia Levy, MD, PhD, chief medical officer at Foundation Medicine. "Our high-quality tissue and liquid biopsy companion diagnostic tests will allow more patients to access genomic testing, regardless of specimen type, and will simplify complex decisions by generating the best information to enable better decision-making. There is a critical unmet need for first-line treatment options for patients with BRCA-mutated mCRPC, and this combination therapy is an important advancement."
Safety Profile
The most common adverse effects reported with olaparib plus abiraterone included anemia (48%), fatigue (38%), nausea (30%), diarrhea (19%), decreased appetite (16%), lymphopenia (14%), dizziness (14%), and abdominal pain (13%). Eighteen percent of patients needed at least one blood transfusion, and 12% required multiple transfusions.
Study Design
Eligibility for PROpel was limited to patients with metastatic CRPC who were required to have prior orchiectomy and, if not performed, receipt of gonadotropin-releasing hormone analogs. Patients who had previously received systemic therapy for metastatic CRPC were excluded. Prior docetaxel was not an excluding factor.
