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FDA Approves Companion Diagnostic, FoundationOne Liquid CDx, for Olaparib in Prostate Cancer

Monday, November 09, 2020
The FDA has approved the FoundationOne Liquid CDx for use as a companion diagnostic with olaparib (Lynparza), which is indicated for select patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene–mutated metastatic castration-resistant prostate cancer (mCRPC).1,2

The diagnostic will utilize a blood-based biopsy to identify patients with mCRPC who harbor BRCA1, BRCA2, and/or ATM alterations who may be appropriate candidates for treatment with the PARP inhibitor.

“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 [patients with] metastatic prostate cancer, 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.

Previously, in August 2020, the FoundationOne Liquid CDx was approved by the FDA for all solid tumors with multiple diagnostic indications.3,4 The decision was based on analytical and clinical validation trials that collected more than 7500 samples and 30,000 unique variants across over 30 tumor types. When the platform was evaluated across these various tumors, the test demonstrated high sensitivity and specificity, even at the low allele frequencies that were observed in the blood samples that had been collected.

FoundationOne Liquid CDx is a tool that was developed to inform treatment decisions in accordance with FDA-approved labeling and professional guidance for patients with solid tumors. The assay is indicated for use as a companion diagnostic to identify which patients are appropriate for FDA-approved targeted therapies, such as rucaparib (Rubraca), which was recently FDA approved for select adult patients with mCRPC harboring a BRCA1/2 mutation, and 3 frontline TKIs in non–small cell lung cancer (NSCLC).

In October 2020, the FDA approved the FoundationOne Liquid CDx assay for use as a companion diagnostic for 3 targeted therapies in several tumor types: alpelisib (Piqray) in advanced or metastatic breast cancer, rucaparib in advanced ovarian cancer, and alectinib (Alcensa) in a specific type of NSCLC. The regulatory agency also allowed for a label expansion for the test to report additional select copy number alterations and genome rearrangements.

In May 2020, olaparib received regulatory approval for patients with deleterious or suspected deleterious germline or somatic HRR gene–mutated mCRPC who have progressed on previous treatment with either enzalutamide (Xtandi) or abiraterone acetate (Zytiga) based on data from the phase 3 PROfound trial.

Data from the trial demonstrated that treatment with olaparib reduced the risk of disease progression or death by 66% compared with abiraterone acetate or enzalutamide (hazard ratio [HR], 0.34; 95% CI, 0.25-0.47; P <.0001) in patients with BRCA1/2- or ATM-mutated mCRPC. In the entire population of patients with mCRPC who had mutations in genes for BRCA1/2, ATM, CDK12, or 11 other HRR-mutated genes, the PARP inhibitor resulted in 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).

The PARP inhibitor was also found to result in a statistically significant improvement in overall survival (OS) in patients with mCRPC who harbored BRCA1/2 or ATM mutations. In this subset, the median OS with olaparib was 19.1 months versus 14.7 months with enzalutamide or abiraterone (HR, 0.69; 95% CI, 0.50-0.97; P =.0175).

Cohort A of the trial comprised patients with alterations either in BRCA1/2 or ATM (n = 245), while cohort B included patients with other HRR gene mutations, such as BARD1, BRIP1, CDK12, CHEK1/2, FANCL, PALB2, PPP2R2A, RAD51B/C/D, or RAD54L. Patients were randomized 2:1 to receive either olaparib or physician’s choice of abiraterone plus prednisone or enzalutamide.

Additional results showed that the confirmed overall response rate (ORR) with olaparib in cohort A was 33.3% versus 2.3% with the antiandrogen agents (odd ratio [OR], 20.86; 95% CI, 4.18-379.18; P <.0001).

Moreover, the median time to progression had not yet been reached with the PARP inhibitor versus 9.92 months with the antiandrogen agents, translating to a 56% reduction in the risk of pain progression (HR, 0.44; 95% CI, 0.22-0.91; P =.0192). In this cohort, the median radiographic progression-free survival (rPFS) was 7.4 months with olaparib versus 3.6 months with hormonal therapy. In cohort B, the HR for rPFS was 0.88 by blinded review (95% CI, 0.58-1.36).

In both cohorts A and B, the median rPFS was 5.8 months with the PARP inhibitor versus 3.5 months with the antiandrogen agents. Additionally, in the combined cohorts, the ORRs with olaparib and the antiandrogen agents were 21.7% and 4.5%, respectively (OR, 5.93; 95% CI, 2.01-25.40; P =.0006). The median OS was 17.5 months and 14.3 months with olaparib and the hormonal agents, respectively (HR, 0.67; 95% CI, 0.49-0.9; P =.0063).

In May 2020, the tissue-based comprehensive genomic profiling test, FoundationOne CDx, was approved for use as a companion diagnostic for olaparib, according to Foundation Medicine, Inc.

“[Today’s] 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 in the release.

1. Foundation Medicine expands indication for FoundationOne Liquid CDx to be used as a companion diagnostic for LYNPARZA. News release. Foundation Medicine, Inc. November 9, 2020. Accessed November 9, 2020.
2. Lynparza approved in the US for HRR gene-mutated metastatic castration-resistant prostate cancer. News release. AstraZeneca. May 20, 2020. Accessed November 9, 2020.
3. FDA approves FoundationOne Liquid CDx to serve as Rubraca (rucaparib) companion diagnostic to identify eligible patients with BRCA1/2-mutant, metastatic castration-resistant prostate cancer (mCRPC). News release. Clovis Oncology, Inc. August 26, 2020. Accessed November 9, 2020.
4. FDA approves Foundation Medicine’s FoundationOne Liquid CDx, a comprehensive pan-tumor liquid biopsy test with multiple companion diagnostic indications for patients with advanced cancer. News release. Foundation Medicine, Inc. August 26, 2020. Accessed November 9, 2020.

This article was originally published on OncLive as, "FDA Approves FoundationOne Liquid CDx as Companion Diagnostic for Olaparib in Prostate Cancer."

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