FDA Approves Frontline Erlotinib With Novel Companion Diagnostic for Advanced NSCLC

Alberto Gutierrez, PhD

The FDA concurrently approved erlotinib (Tarceva) along with a companion diagnostic to be used together in the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) harboring distinct EGFR mutations.

The cobas EGFR Mutation Test is the first EGFR-specific companion diagnostic to be approved by the FDA. This test identifies patients with specific alterations in the EGFR gene, which denote sensitivity to treatment with erlotinib, an agent that reversibly inhibits the EGFR tyrosine kinase.

“The approval of the cobas EGFR Mutation Test will allow physicians to identify non-small cell lung cancer patients who are candidates for receiving Tarceva as first line therapy,” said Alberto Gutierrez, PhD, director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health, in a statement. “Companion diagnostics play an important role in determining which therapies are the safest and most effective for a particular patient.”

According to the FDA, the approval was based on findings from the open-label phase III European Tarceva versus Chemotherapy (EURTAC) trial. This trial analyzed 173 patients with advanced non-squamous NSCLC categorized by mutations in the EGFR tyrosine kinase domain. These alterations included exon 19 deletions and exon 21 L858R mutations, which account for approximately 90% of all EGFR mutations in lung cancer.

In the EURTAC trial, patients were evenly randomized to receive erlotinib or a standard two-drug chemotherapy regimen in the front-line setting. The median progression-free survival (PFS) in the erlotinib arm was 10.4 months compared with 5.2 months in the chemotherapy arm (P = .0030), according to an independent review committee.

The main adverse event reported with erlotinib treatment was rash. However, only 6% of patients treated with erlotinib had treatment-related severe adverse events compared with 20% receiving chemotherapy.

The FDA first approved Erlotinib in 2004 for the treatment of NSCLC patients after failure on at least one prior chemotherapy regimen. That approval was expanded in 2010 for use as a maintenance therapy for patients with locally advanced or metastatic NSCLC whose disease had not progressed after four cycles of platinum-based chemotherapy in the first-line. Erlotinib was also approved for the treatment of locally advanced, unresectable, or metastatic pancreatic cancer in combination with gemcitabine in 2005.

Pleasanton, California-based Roche Molecular Systems will manufacture the cobas EGFR mutation test. Erlotinib is co-marketed as Tarceva by California-based Genentech, a member of the Roche Group and OSI Pharmaceuticals of Farmingdale, New York.