FDA approves liquid biopsy as companion diagnostic for olaparib in prostate cancer

FoundationOneLiquid CDx will identify HRR alterations, such as BRCA1, BRCA2, and ATM, that make a patient eligible for olaparib.

The FDA has approved FoundationOneLiquid CDx for use as a companion diagnostic with the PARP inhibitor olaparib (Lynparza), which is approved by the FDA for the treatment of patients with homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC).1

The pan-tumor liquid biopsy test examines over 300 cancer-related genes in a patient’s blood sample to inspect for deleterious alterations. FoundationOneLiquid CDx will identify HRR alterations, such as BRCA1, BRCA2, and ATM, that make a patient eligible for olaparib.

“With this latest companion diagnostic approval, physicians now have the option to choose either tissue or liquid-based comprehensive genomic testing based on their patients’ need and condition. Since tissue availability can be an issue for some metastatic prostate cancer patients, blood-based testing is an important option to consider and critically important for informing patient care,” Brian Alexander, MD, MPH, chief medical officer at Foundation Medicine, stated in a press release.

“The approval of this companion diagnostic will allow more patients to access genomic testing, regardless of specimen type, and provide oncologists with another tool to guide personalized treatment decisions,” added Alexander.

The FDA approved olaparib in May 2020 for the treatment of adult patients with deleterious or suspected deleterious germline or somatic HRR gene–mutated metastatic mCRPC who have progressed following prior treatment with enzalutamide (Xtandi) or abiraterone acetate (Zytiga).

The approval was supported by the phase 3 PROfound trial, in which the risk of death was reduced by 31% with olaparib compared with abiraterone or enzalutamide (HR, 0.69; P <.0001) in patients with mCRPC harboring an alteration in BRCA1BRCA2, or ATM.2 Olaparib also reduced the risk of disease progression or death by 66% (HR, 0.34; P <.001).

The PROfound trial enrolled patients with mCRPC who had alterations in at least 1 of 15 prespecified genes with a direct or indirect role in HRR and whose disease had progressed during previous treatment with a next-generation hormonal agents.

Cohort A (n = 245) consisted of patients with at least 1 alteration in BRCA1BRCA2, or ATM, while cohort B (n = 142) comprised patients with at least one alteration in any of the other 12 prespecified genes.

Patients were randomly assigned 2:1 to receive either olaparib or the physician’s choice of enzalutamide or abiraterone. The study allowed patients to cross over from the control arm to receive olaparib at disease progression. In cohort A, 162 patients received olaparib and 83 patients were assigned to control therapy. In cohort B, 94 patients received olaparib while 48 patients were in the control arm.

The median OS was superior with olaparib compared with control therapy in cohort A (19.1 months vs 14.7 months; HR, 0.69; P = .02) and cohort B (14.1 months vs 11.5 months; HR, 0.96). Also of note, in cohort A the median PFS was 7.4 months with olaparib compared with 3.6 months in the control arm (HR, 0.34; <.001)

In cohort A, 67% (56/83) of patients on the control arm crossed over at progression, and a crossover-adjusted analysis showed an even greater survival benefit for olaparib, with a hazard ratio for OS of 0.42.

Across the study, the most common adverse events among patients receiving olaparib group were anemia (39%), nausea (36%), and fatigue or asthenia (32%). Treatment with olaparib was discontinued because of anemia in 7% of patients and because of neutropenia, thrombocytopenia, nausea, vomiting, or fatigue or asthenia in 1% of the patients for each.


1. Foundation Medicine Expands Indication for FoundationOne®Liquid CDx to be used as a Companion Diagnostic for LYNPARZA®. Posted online November 9, 2020. https://bit.ly/3n7hpWC. Accessed November 9, 2020.

2. Hussain M, Mateo J, Fizazi K, et al. Survival with olaparib in metastatic castration-resistant prostate cancer [published online September 20, 2020]. N Engl J Med. doi:10.1056/NEJMoa2022485

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