cobas EGFR Mutation Test v2

On June 1, 2016, 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 recptor (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.

The approval was based on a multicenter, open-label, randomized, Phase III study, to evaluate the efficacy and safety of Tarceva versus gemcitabine plus cisplatin as first-line treatment for stage IIIB/IV NSCLC patients (ENSURE study). Patients entering the ENSURE study had tumor tissue specimens that tested positive for the EGFR exon 19 deletion or L858R mutations as determined by the cobas EGFR Mutation Test v1. Five hundred seventeen of the 601 (86.0%) patients screened for the ENSURE study with valid cobas EGFR Mutation Test v1 test results had available plasma samples available. Of the patients enrolled, 98.6% (214/217) had a plasma sample available for testing. The agreement between the cobas EGFR Mutation Test v2 in plasma and thecobas EGFR Mutation Test v1 in tissue was evaluated for detection of EGFR mutations (Ex. 19del and L858R mutations) in NSCLC patients screened for participation in ENSURE. In 76.7% (70.5%, 81.9%) of tissue-positive specimens, plasma was also positive for an EGFR mutation. Plasma was negative for EGFR mutation in 98.2% (95.4%, 99.3%) of tissue-negative cases. The drug efficacy of TARCEVA, based on the cobas EGFR Mutation Test v2 in plasma, was evaluated by bridging to the drug efficacy based on the cobas EGFR Mutation Test v1 in tissue in the ENSURE study.

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

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online athttp://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).