FDA Green Lights Companion Diagnostics for Olaparib Plus Abiraterone Acetate in BRCA+ mCRPC

US FDA

The FDA has approved FoundationOne^® CDx and FoundationOne Liquid CDx for use as companion diagnostics for olaparib (Lynparza) plus abiraterone acetate (Zytiga) and prednisone or prednisolone for the treatment of adult patients with deleterious or suspected deleterious BRCA-mutated metastatic castration-resistant prostate cancer (mCRPC).¹

The regulatory agency previously approved FoundationOne CDx as a companion diagnostic for olaparib in the treatment of patients with mCRPC harboring homologous recombination repair (HRR) gene alterations. FoundationOne Liquid CDx was also previously approved as a companion diagnostic for olaparib in patients with mCRPC harboring BRCA1, BRCA2, or ATM alterations.

“This approval reinforces the importance of testing for genomic mutations at metastatic diagnosis to help guide treatment decisions,” Mia Levy, MD, PhD, chief medical officer at Foundation Medicine, stated in a news release. “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.”

In May 2023, the FDA approved olaparib in combination with abiraterone acetate and prednisone or prednisolone for the treatment of patients with deleterious or suspected deleterious BRCA-mutated mCRPC, as determined by an FDA-approved companion diagnostic test.²

The approval was supported by data from an exploratory subgroup analysis of the phase 3 PROpel trial (NCT03732820), which showed that patients harboring BRCA mutations treated with olaparib plus abiraterone acetate and prednisone or prednisolone (n = 47) experienced a median radiological progression-free survival (rPFS) that was not reached (NR; 95% CI, NR-NR) compared with 8 months (95% CI, 6-15) in those given placebo plus abiraterone acetate and prednisone or prednisolone (n = 38; HR, 0.24; 95% CI, 0.12-0.45).³ The median overall survival (OS) in this population was also NR (95% CI, NR-NR) in the olaparib arm vs 23 months (95% CI, 18-34) in the placebo arm (HR, 0.30; 95% CI, 0.15-0.59).

Although statistically significant improvements in rPFS and OS were observed for the olaparib regimen vs the placebo regimen in the intention-to-treat (ITT) population, findings from an exploratory subgroup analysis revealed that the hazard ratios for rPFS and OS were 0.77 (95% CI, 0.63-0.96) and 0.92 (95% CI, 0.74-1.14), respectively, in the non–BRCA-mutated population (n = 711); this suggests that the ITT population improvements were primarily attributed to outcomes for those with BRCA-mutated disease.

PROpel was a randomized, double-blind, placebo-controlled, multicenter study that enrolled patients at least 18 years of age with histologically or cytologically confirmed prostate adenocarcinoma with at least 1 documented metastatic lesion.⁴ Prior treatment for mCRPC was not allowed, except for androgen deprivation therapy and first-generation antiandrogen agents with a 4-week washout period. Neoadjuvant or adjuvant docetaxel for localized for metastatic hormone-sensitive prostate cancer (mHSPC) was permitted.

Patients were randomly assigned 1:1 to receive olaparib at 300 mg twice per day plus abiraterone acetate at 1000 mg per day (n = 399) or placebo plus abiraterone acetate (n = 397).³ Prednisone or prednisolone was given to all patients at 5 mg twice per day. Treatment with olaparib or placebo continued until radiological disease progression or unacceptable toxicity.

Stratification factors included type of distant metastases at baseline (bone only vs visceral vs other) and docetaxel treatment for mHSPC (yes vs no).³ FoundationOne CDx and FoundationOne Liquid CDx were used to determine HRR mutation status during the study.⁴

Imaging-based PFS served as the trial’s primary end point, and OS was a key secondary end point.⁴

Regarding safety, the most common adverse effects reported in at least 10% of patients treated in the olaparib arm included anemia (48%), fatigue (38%), nausea (30%), diarrhea (19%), reduced appetite (16%), lymphopenia (14%), dizziness (14%), and abdominal pain (13%).²

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 3, 2024. https://www.foundationmedicine.com/press-release/fda-approval-cdxs-lynparza-brca-mcrpc
2. FDA approves olaparib with abiraterone and prednisone (or prednisolone) for BRCA-mutated metastatic castration-resistant prostate cancer. FDA. 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
3. Olaparib (Lynparza). Prescribing information. AstraZeneca. Updated November 2023. Accessed September 3, 2024. https://den8dhaj6zs0e.cloudfront.net/50fd68b9-106b-4550-b5d0-12b045f8b184/00997c3f-5912-486f-a7db-930b4639cd51/00997c3f-5912-486f-a7db-930b4639cd51_viewable_rendition__v.pdf
4. Clarke NW, Armstrong AJ, Thiery-Vuillemin A, et al. Abiraterone and olaparib for metastatic castration-resistant prostate cancer. NEJM Evid. 2022;1(9):EVIDoa2200043. doi:10.1056/EVIDoa2200043