Advancing Biomarker Testing for Four Common Cancers
The FDA granted approval to expand the use of a minimally invasive biomarker test to identify certain patients with ovarian, lung, breast, or prostate cancer eligible for treatment with specific molecularly targeted therapeutics.
The U.S. Food and Drug Administration (FDA) approved the expanded use of a next-generation sequencing assay, FoundationOne Liquid CDx as a companion diagnostic to test for specific genetic mutations found in some ovarian, lung, breast, and prostate cancers. The test uses blood samples to look for specific molecular signatures in tumors and identify patients eligible for treatment with specific molecularly targeted therapeutics.
The test can detect various alterations across more than 300 genes and has been approved as a companion diagnostic for over 20 targeted therapeutics. The latest FDA approvals represent another step in expanding the use of liquid biopsies in cancer treatment as well as propelling more widespread implementation of genomic testing to advance cancer precision medicine.
The first indication in this expanded approval is to look for mutations in the BRCA1 and BRCA2 genes in patients with ovarian cancer who could be candidates for treatment with rucaparib (Rubraca). This agent is known as a PARP inhibitor because it disrupts the function of PARP proteins that cancer cells use to repair damaged DNA and continue thriving. According to federal statistics, there will be close to 22,000 new cases of ovarian cancer in 2020 and almost 14,000 deaths
Another genetic target included in this approval focuses on identifying mutations in the ALK gene in patients with non-small cell lung cancer for potential treatment with alectinib (Alecensa), a targeted therapeutic that can stop cancer cells from multiplying and surviving. Lung cancer remains the leading cause of cancer death in the United States and throughout the world. Non-small cell lung cancer is the most common form of the disease and according to the National Cancer Institute (NCI), about 5 percent of such tumors are ALK-positive.
The third expanded use for FoundationOne CDx is to identify mutations in the PIK3CA gene in patients with breast cancer. These genetic alterations cause cells to grow uncontrollably and patients who have them may benefit from treatment with the targeted agent alpelisib (Piqray). Studies estimate that PIK3CA mutations affect about 20-30 percent of all breast cancers and are most common in patients with hormone receptor-positive, HER2-negative breast cancer, that is, breast cancer that grows in response to estrogen and that does not have the protein HER2 on the surface of the cancer cells.
The fourth cancer covered in this approval is prostate cancer. The FDA approved the test to identify mutations in three genes associated with metastatic castration-resistant prostate cancer, which is cancer that continues to grow and spread in spite of using hormone therapy to suppress it. Along with mutations in the BRCA1 and BRCA2 genes, the diagnostic test looks for alterations in the ATM gene, which provides instructions for making a protein that plays a central role in cell division and DNA repair. Patients with certain genetic aberrations in these three genes may be eligible for treatment with olaparib (Lynparza), an agent that takes aim at mutations associated with DNA damage response and repair found in many patients with prostate cancer. These alterations, particularly those in the BRCA2 gene, are known to be associated with more aggressive forms of the disease. DNA damage repair defects account for about 25 percent of the genetic alterations found in prostate cancers, with BRCA2 mutations representing the most common defects. According to the NCI, there will be almost 192,000 new cases of prostate cancer diagnosed in 2020 and over 33,000 deaths from the disease.
The expanded indications for FoundationOne Liquid CDx as a companion diagnostic for treatment with rucaparib, alpelisib, alectinib, and olaparib were based on performing retrospective testing on blood samples from patients in the four clinical trials that supported the initial approval of these four molecularly targeted therapeutics to treat the associated cancers.
The FDA approvals for the expanded use of FoundationOne CDx in ovarian, lung, and breast cancer was rendered on October 26, 2020. The approval for its use in prostate cancer was issued on November 6, 2020.