FDA Approves FoundationOne Liquid CDx as Companion Test for Lynparza in mCRPC Patients

FDA Approves FoundationOne Liquid CDx as Companion Test for Lynparza in mCRPC Patients

The U.S. Food and Drug Administration (FDA) has approved FoundationOne Liquid CDx to be used as a companion diagnostic test to identify men with metastatic castration-resistant prostate cancer (mCRPC) who are likely to benefit from treatment with Lynparza (olaparib).

Developed by Foundation Medicine, the test is a blood-based biopsy assessment approved by the FDA to analyze the genetic signature of solid tumors, with the goal of identifying patients who may benefit from certain FDA-approved targeted cancer therapies.

Capable of detecting alterations in more than 300 cancer-related genes, FoundationOne Liquid CDx is currently the most comprehensive companion diagnostic test for solid tumors available on the market.

The U.S. agency has now specifically approved the test to identify men with mCRPC carrying mutations in BRCA and/or ATM DNA repair genes, who are likely to respond to Lynparza. FoundationOne CDx, the company’s tissue-based genomic profile test, was also approved earlier this year to be used as a companion diagnostic test for Lynparza.

“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,” Brian Alexander, MD, chief medical officer at Foundation Medicine, said in a press release. “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.”

“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,” he added.

Jointly developed by AstraZeneca and Merck (known as MSD outside North America), Lynparza is an oral targeted cancer therapy approved in the U.S. and Europe to treat men with mCRPC carrying mutations in certain DNA repair genes — BRCA and ATM in the U.S., and BRCA in Europe.

The therapy works by blocking the activity of PARP, an enzyme that is involved in DNA repair. By inhibiting PARP, Lynparza increases the vulnerability of cancer cells to DNA damage, effectively restricting their proliferation and survival. The medication has also been found to be particularly effective in patients carrying mutations in certain DNA repair genes, including BRCA1 and BRCA2.

Lynparza’s approval in the U.S. and Europe was based on data from the PROfound Phase 3 trial (NCT02987543), which enrolled a total of 387 men with mCRPC, including 245 carrying mutations in BRCA and/or ATM DNA repair genes, whose disease progressed while receiving treatment with the hormone therapies Xtandi (enzalutamide) or Zytiga (abiraterone acetate).

This study, which was supported by Foundation Medicine, was the largest Phase 3 trial to date assessing the presence of mutations in DNA repair genes in tumor tissue samples taken from mCRPC patients.

The main goal of the trial was to determine whether Lynparza is superior to Xtandi or Zytiga at prolonging the time these men lived without showing signs of disease progression on regular imaging scans — a measure called radiographic progression-free survival — in the subgroup of patients with BRCA or ATM mutations.

Top-line data from the study showed Lynparza more than doubled that time compared with hormone therapies (7.4 months vs. 3.6 months), corresponding to a 66% decrease in the risk of radiographic disease progression or death.

In this subset of patients, Lynparza was also associated with better response rates (33% vs. 2%), and was more effective than hormone therapy at delaying pain worsening and lowering the levels of prostate-specific antigen, a prostate cancer biomarker.

Final data from the study showed that after a median follow-up of nearly two years, Lynparza prolonged the time men with BRCA or ATM mutations lived to 19.1 months compared with 14.7 months for those on hormone therapy, lowering the risk of death by 31%.

Lynparza also lowered the risk of death in the overall population of men enrolled in the study. However, these differences did not reach statistical significance.

The therapy’s safety profile was also found to be consistent with that from previous studies. The most common side effects observed in PROfound included anemia, nausea, fatigue, low appetite, diarrhea, and vomiting.

With the addition of Lynparza, FoundationOne Liquid CDx is now approved as a companion diagnostic test for seven FDA-approved targeted cancer therapies across four types of solid tumors, including prostate, ovarian, breast, and non-small cell lung cancer.