FDA Approves FoundationOne Tests for Olaparib Combo in BRCA-Mutated mCRPC

The approval of the companion diagnostics follows the 2023 FDA approval of olaparib in combination with abiraterone and prednisone or prednisolone in patients with BRCA-mutated metastatic CRPC based on results of the phase 3 PROpel trial (NCT03732820).

The FDA has granted approval to FoundationOne®CDx and FoundationOne®Liquid CDx as companion diagnostics for olaparib (Lynparza) plus abiraterone and prednisone for the treatment of adults with deleterious or suspected deleterious BRCA-mutated metastatic castration-resistant prostate cancer (CRPC), according to a press release from the developer, Foundation Medicine, Inc.¹

Previously, the FDA had approved the utilization of FoundationOne CDx for the identification of patients with metastatic CRPC with homologous recombination repair (HRR) gene alterations and FoundationOne Liquid CDx for the identification of patients with disease harboring BRCA1, BRCA2, or ATM alterations.

“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, in the press release.¹ “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 [metastatic] CRPC, and this combination therapy is an important advancement.”

According to the press release, the FoundationOne CDx and FoundationOne Liquid CDx tests both analyze more than 300 cancer-related genes to provide genomic insights on patients undergoing diagnostic testing.

“This is an important milestone for [patients] with aggressive prostate cancer,” said Courtney Bugler, president and chief executive officer of ZERO Prostate Cancer, following the FDA approval.1 “Biomarker testing is an important tool for patients and families to help facilitate personalized treatment decision-making.”

The approval of the companion diagnostics follows the 2023 FDA approval of olaparib in combination with abiraterone and prednisone or prednisolone in patients with BRCA-mutated metastatic CRPC based on results of the phase 3 PROpel trial (NCT03732820).²

The primary end point of PROpel was investigator-assessed radiological progression-free survival (rPFS) per RECIST v1.1 criteria for soft tissue and Prostate Cancer Working Group criteria for bone lesions, with overall survival (OS) being a secondary end point. A statistically significant improvement in rPFS was seen in patients who received olaparib with abiraterone compared with those who received abiraterone alone in the intent-to-treat population.

In an exploratory subgroup analysis of patients with BRCA mutations—11% of the intent-to-treat population—the median rPFS was not reached in the olaparib arm vs 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). These findings were potentially indicative of the presence of BRCA mutations being associated with improved radiological PFS.

In terms of overall survival, the hazard ratio for patients with BRCA mutations was 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).

In terms of the 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.

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.

References

1. U.S. Food and Drug Administration approves FoundationOne®CDx and FoundationOne®Liquid CDx as companion diagnostics for Lynparza® (olaparib) in combination with abiraterone for patients with BRCA-mutated metastatic castration-resistant prostate cancer. News Release. Foundation Medicine. September 3, 2024. Accessed September 4, 2024. https://tinyurl.com/2s4cyc8s
2. FDA approves olaparib with abiraterone and prednisone (prednisolone) for BRCA-mutated metastatic castration-resistant prostate cancer. News release. FDA. May 31, 2023. Accessed September 4, 2024. https://bit.ly/3C2UVzg