FDA approves companion diagnostic for olaparib/abiraterone in BRCA+ mCRPC

The FDA has approved the tissue-based FoundationOne CDx and blood-based FoundationOneLiquid CDx tests for use as companion diagnostics in identifying patients with deleterious or suspected deleterious BRCA-mutated metastatic castration-resistant prostate cancer (mCRPC) who may benefit from treatment with olaparib (Lynparza) in combination with abiraterone acetate (Zytiga) and prednisone or prednisolone, Foundation Medicine announced in a news release.¹

Foundation Medicine now has 7 FDA-approved prostate cancer indications for their companion diagnostics.

“This approval reinforces the importance of testing for genomic mutations at metastatic diagnosis to help guide treatment decisions,” said Foundation Medicine’s chief medical officer Mia Levy, MD, PhD, in the news 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 castration-resistant prostate cancer, and this combination therapy is an important advancement.”

This announcement follows an FDA decision earlier this year to grant approval to the company’s liquid biopsy test, FoundationOneLiquid CDx, for use as a companion diagnostic in identifying patients with BRCA-positive mCRPC who may benefit from treatment with niraparib and abiraterone acetate dual action tablets (Akeega). FoundationOne CDx, the tissue-based comprehensive genomic profiling test, was also granted FDA approval for the same therapy and indication in August 2023.

With the recent FDA approvals for FoundationOne CDx and FoundationOneLiquid CDx, Foundation Medicine now has 7 FDA-approved prostate cancer indications for their companion diagnostics.²

“This is an important milestone for men with aggressive prostate cancer,” added Courtney Bugler, president and CEO of ZERO Prostate Cancer, in the news release.1 “Biomarker testing is an important tool for patients and families to help facilitate personalized treatment decision making, and we applaud Foundation Medicine for these additional companion diagnostic indications.”

Data on olaparib/abiraterone

The FDA granted approval to the combination of olaparib plus abiraterone and prednisone or prednisolone for the treatment of adult patients with deleterious or suspected deleterious BRCA-mutated mCRPC, as determined by an FDA approved companion diagnostic test, in May 2023.

The approval was primarily supported by data from the phase 3 PROpel trial (NCT03732820), in which results from the intent-to-treat (ITT) population demonstrated that the addition of olaparib to frontline abiraterone acetate and prednisone/prednisolone significantly improved radiographic progression-free survival (rPFS) compared with abiraterone and prednisone/prednisolone alone in patients with mCRPC.³

In the overall ITT population, the median investigator-assessed rPFS was 24.8 months with olaparib/abiraterone vs 16.6 months with placebo/abiraterone, translating to a 34% reduction in the risk of radiographic disease progression or death (HR, 0.66; 95% CI, 0.54-0.81; P < .0001).⁴

Data from the final prespecified overall survival (OS) analysis for the ITT population showed that the median OS was 42.1 months in the abiraterone/olaparib cohort vs 34.7 months in the abiraterone/placebo cohort, translating to a 19% reduction in the risk of death (HR, 0.81; 95% CI, 0.67-1.00; P = .0544). The maturity for survival was 47.9%. The results were not statistically significant.⁵

The FDA decision to limit the approval to the BRCA–positive population was based on a subanalysis that focused solely on the 11% (n = 85) of patients in the PROpel trial with confirmed BRCA mutations. In this subgroup, the addition of olaparib to abiraterone led to a 76% reduction in the risk of disease progression or death vs abiraterone alone (HR, 0.24) and a 70% reduction in the risk of death (HR, 0.3). The median rPFS was not reached in the olaparib plus abiraterone arm compared with 8 months (95% CI, 6-15) for those receiving placebo with abiraterone.

In contrast, among patients without BRCA mutations (n = 711), the addition of olaparib only led to a 23% reduction in the risk of disease progression or death (HR, 0.77) and no reduction in the risk of death (HR, 0.96).

Regarding safety, adverse events (AEs) occurred in 97.2% and 94.9% of olaparib/abiraterone- and placebo/abiraterone-treated patients, respectively. Grade 3 or higher AEs occurred in 47.2% and 38.4% of patients, respectively. AE-related deaths occurred in 4.0% (n = 16) of those on the olaparib arm compared with 4.3% (n = 17) of patients on the placebo arm.

Overall, the international, double-blind, phase 3 PROpel trial included 796 patients with mCRPC in the first-line setting. Patients were randomly assigned 1:1 to receive olaparib at 300 mg twice daily plus abiraterone at 1000 mg daily (n = 399) or placebo and abiraterone at 1000 mg daily (n = 397). The primary end point was rPFS, with OS as an additional end point.

References

1. U.S. Food and Drug Administration approves FoundationOne CDx and FoundationOneLiquid 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, Inc. Published online and accessed September 3, 2024. https://www.foundationmedicine.com/press-release/fda-approval-cdxs-lynparza-brca-mcrpc

2. Portfolio. Foundation Medicine. Accessed September 3, 2024. https://www.foundationmedicine.com/portfolio

3. FDA approves olaparib with abiraterone and prednisone (or prednisolone) for BRCA-mutated metastatic castration-resistant prostate cancer. May 31, 2023. Accessed September 3, 2024. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-olaparib-abiraterone-and-prednisone-or-prednisolone-brca-mutated-metastatic-castration

4. Clarke NW, Armstrong AJ, Thiery Vuillemin A, et al; PROpel Investigators. Abiraterone and olaparib for metastatic castration-resistant prostate cancer. NEJM Evid. 2022;1(9). doi:10.1056/EVIDoa2200043

5. Clarke NW, Armstrong AJ, Thiery Vuillemin A, et al. Final overall survival (OS) in PROpel: abiraterone (abi) and olaparib (ola) versus abiraterone and placebo (pbo) as first-line (1L) therapy for metastatic castration-resistant prostate cancer (mCRPC). J Clin Oncol. 2023;41(suppl 6):LBA16. doi:10.1200/JCO.2023.41.6_suppl.LBA16