FDA Approves Multiple Companion Diagnostics for Olaparib in HRR+ mCRPC

The FDA has approved the FoundationOneCDx and BRACAnalysis CDx tests as companion diagnostics to identify patients with metastatic castration-resistant prostate cancer with homologous recombination repair mutations, making them eligible for treatment with the PARP inhibitor olaparib.

The FDA has approved the FoundationOneCDx and BRACAnalysis CDx tests as companion diagnostics to identify patients with metastatic castration-resistant prostate cancer (mCRPC) with homologous recombination repair (HRR) mutations, making them eligible for treatment with the PARP inhibitor olaparib (Lynparza).1,2

The FDA recently approved olaparib for the treatment of adult patients with deleterious or suspected deleterious germline or somatic HRR gene–mutated mCRPC who have progressed following prior treatment with enzalutamide (Xtandi) or abiraterone acetate (Zytiga).3
Regarding the FoundationOneCDx test, Brian Alexander, MD, MPH, chief medical officer at Foundation Medicine, stated in a press release, “This therapy and companion diagnostic approval underscores the value of comprehensive genomic profiling in advanced cancer patients as it validates our ability to identify alterations in the 14 HRR pathway genes within FoundationOne CDx’s 324 gene panel that indicate a patient may be eligible for treatment with Lynparza, a process not possible through single gene or hot spot testing. This is an important advancement for patients with HRR-mutated metastatic castration-resistant prostate cancer, as there have previously been limited treatment options available for this specific condition.”

Todd Cohen, MD, board-certified urologist and vice president of Medical Affairs for Myriad Urology, commented in a separate press release on the BRACAnalysis CDx test. “Studies have demonstrated that PARP inhibitors are highly effective in men with BRCA1/BRCA2 mutations, in addition to other mutations in HRR pathways. Once we identify who these men are, they will have more options for treatment. NCCN guidelines recommend that men with metastatic castration-resistant prostate cancer undergo genetic testing alongside an assessment of HRR gene mutations in the tumor.”

The approval of olaparib in HRR-mutant mCRPC was based on findings from the phase 3 PROfound trial, which showed that the PARP inhibitor olaparib induced a 66% reduction in the risk of disease progression or death compared with abiraterone acetate (Zytiga) or enzalutamide (Xtandi; HR, 0.34; 95% CI, 0.25-0.47; P <.0001) in patients with BRCA1/2- or ATM-mutant mCRPC.

Overall, the trial showed that olaparib demonstrated a 51% reduction in the risk of disease progression or death versus either of the antiandrogen agents (HR, 0.49; 95% CI, 0.38-0.63; P <.0001) in the entire population of patients with HRR-mutant mCRPC who had mutations in genes for BRCA1/2ATMCDK12, or 11 other HRR-mutated genes.

Olaparib also led to a statistically significant improvement in overall survival (OS) in patients with BRCA1/2- or ATM-mutant mCRPC. In this population, the median OS was 19.1 months with olaparib compared with 14.7 months with enzalutamide or abiraterone (HR, 0.69; 95% CI, 0.50-0.97; P = .0175).

Regarding safety, the tolerability of olaparib was consistent with what has been previously observed in prior studies. The most common adverse events (AEs), occurring at ≥20%, were anemia (47%), nausea (41%), fatigue/asthenia (41%), decreased appetite (30%), and diarrhea (21%). The most common grade ≥3 AEs, occurring at ≥1%, were anemia (22%), fatigue/asthenia (3%), vomiting (2%), dyspnea (2%), urinary tract infection (2%), pulmonary embolism (2%), decreased appetite (1%), diarrhea (1%), back pain (1%), and nausea (%). A total of 18% of patients who were treated with olaparib discontinued treatment due to AEs.


  1. Foundation Medicine Receives FDA Approval for FoundationOne®CDx as the Companion Diagnostic for LYNPARZA® to Identify Patients with HRR-Mutated Metastatic Castration-Resistant Prostate Cancer. https://bit.ly/2Zt33qG. Published May 20, 2020. Accessed May 20, 2020.
  2. Myriad Receives FDA Approval of BRACAnalysis CDx® as a Companion Diagnostic for Lynparza® in HRR-mutated Metastatic Castration-Resistant Prostate Cancer. Published May 20, 2020. https://bit.ly/2LNE09K. Accessed May 20, 2020.
  3. Lynparza Highlights of Prescribing Information. FDA. Updated May 19, 2020. https://bit.ly/2WLJt7u. Accessed May 19, 2020.
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