FDA Approves First Liquid Biopsy Test for Use in Non-Small Cell Lung Cancer

| June 1, 2016

adenosquamousExciting news today from FDA with news of approval of first liquid biopsy test for use in non-small cell lung cancer.  The cobas EGFR test is already approved for use in formalin-fixed paraffin-embedded (FFPE) tissue. This new use is intended for detection of these specific mutations in circulating-free tumor DNA (cfDNA) from plasma for first line therapy with erlotinib. I think this will be the first of many approvals for specific tumor mutations to guide therapy when “tissue is an issue” and biopsy collection and/or sufficient tumor volume in FFPE samples precludes definitive testing.  While patients who may be positive for mutations by the liquid biopsy method are candidates for therapy, negative results should be confirmed with biopsy on FFPE testing for EGFR mutations.

Today, the U. S. Food and Drug Administration approved cobas® EGFR Mutation Test v2 (Roche Molecular Systems, Inc.) using plasma specimens as a companion diagnostic test for the detection of exon 19 deletions or exon 21 (L858R) substitution mutations in the epidermal growth factor receptor (EGFR) gene to identify patients with metastatic non-small cell lung cancer (NSCLC) eligible for treatment with Tarceva® (erlotinib).  The cobas® EGFR Mutation Test v2 is already approved for this indication using formalin-fixed paraffin-embedded (FFPE) tissue specimens.  The new use is for detection of these specific mutations in circulating-free tumor DNA (cfDNA) isolated from plasma specimens, also called liquid biopsy specimens, to aid physicians in identifying patients who may be treated first with Tarceva® (erlotinib).

This is the first “liquid biopsy test” approved for use by FDA. This new test may benefit patients who may be too ill or are otherwise unable to provide a tumor specimen for EGFR testing.  Patients positive by cobas®EGFR Mutation Test v2 using plasma specimens for the presence of EGFR exon 19 deletions or L858R mutations are candidates for treatment with Tarceva® (erlotinib). Patients who are negative by this test should undergo routine biopsy and testing for EGFR mutations with the FFPE tissue sample type.

Lung cancer is the leading cause of cancer-related death among men and women in the U.S. and, though more common in men, the number of deaths from lung cancer in women is increasing. According to the National Cancer Institute, an estimated 221,200 Americans will be diagnosed with lung cancer, and 158,040 will die from the disease this year. NSCLC is the most common type of lung cancer. NSCLC tumors may shed tumor DNA into a patient’s blood, making it possible to detect specific mutations in blood samples. Testing for tumor DNA using a blood sample is also called a “liquid biopsy.”

“Approvals of liquid biopsy tests make it possible to deliver highly individualized health care for patients,” said Alberto Gutierrez, Ph.D., director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health. “Liquid biopsies also have the potential to allow physicians to identify patients whose tumors have specific mutations in the least invasive way possible.”

With the cobas EGFR Mutation Test v2, the presence of specific NSCLC mutations [exon 19 deletion or exon 21 (L858R) substitution mutations] detected in patients’ blood samples aids in selecting those who may benefit from treatment with Tarceva. However, if such mutations are not detected in the blood, then a tumor biopsy should be performed to determine if the NSCLC mutations are present. Insofar as the test provides positive results, it may benefit patients who may be too ill or are otherwise unable to provide a tumor specimen for EGFR testing.

The efficacy of the cobas EGFR Mutation Test v2 using blood samples was determined by using the test to identify the EGFR mutation status in patients enrolled into a clinical trial whose tumor biopsies were previously confirmed positive for the EGFR exon 19 deletion or L858R mutations as determined by the cobas EGFR Mutation Test v1.

The FDA approved Tarceva in 2004 to treat patients with locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen, and in 2013, the FDA approved it for  the first-line treatment of patients with metastatic non-small cell lung cancer whose tumors having EGFR exon 19 deletions or L858R substitution mutations as detected by an FDA-approved test. The most common side effects of Tarceva are rash, diarrhea, anorexia, fatigue, difficulty breathing (dyspnea), cough, nausea and vomiting. Tarceva is not recommended for use in combination with platinum-based chemotherapy and the drug has not been evaluated as first-line treatment in patients with metastatic NSCLC whose tumors have EGFR mutations other than exon 19 deletions or L858R substitution mutations.

The patients whose plasma results were positive for exon 19 deletion and/or an L858R mutations treated with erlotinib had improved progression-free survival (PFS) compared to those treated with chemotherapy.

The cobas® EGFR Mutation Test v2 for use with plasma test is intended to be used to initially screen patients with metastatic NSCLC for EGFR mutations.  Those patients in whom no exon 19 deletion and/or an L858R mutation is detected in their plasma specimens should then be reflexed to having their EGFR status determined from their FFPE tissue specimen.

This application was approved before the Medical Device User Fee Amendments 2012 (MDUFA III) goal date of August 23, 2016. The cobas® EGFR Mutation Test v2 premarket application (PMA) was granted Priority Review.  Summary of Safety and Effectiveness Data and labeling for the cobas® EGFR Mutation Test v2 will be available in approximately 30 days at: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMA/pma.cfm.

The cobas EGFR Mutation Test v2 is manufactured by Roche Molecular Systems in
Pleasanton, California. Tarceva is manufactured by Astellas Pharma Technologies, Inc. of Norman, Oklahoma and distributed by Genentech Inc., of South San Francisco, California.

Source: FDA

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