FDA Approves Erlotinib (Tarceva) as First-Line Lung Cancer Therapy for Certain Patients

May 17, 2013

The FDA approved a label expansion for erlotinib (Tarceva), along with the cobas EGFR mutation diagnostic test, to include patients untreated metastatic NSCLC patients whose tumors have either a deletion in exon 19 or exon 21 (L858R) substitution mutations in the EGFR gene.

The US Food and Drug Administration (FDA) today approved a companion diagnostic test for erlotinib (Tarceva), an oral cancer drug. The cobas EGFR mutation test detects mutations in the epidermal growth factor receptor (EGFR) gene. Patients with advanced non–small-cell lung cancer (NSCLC) who test positive for an EGFR mutation may be eligible for erlotinib. Erlotinib is a reversible tyrosine kinase inhibitor that targets EGFR. The drug is co-marketed by Genentech, a part of the Roche Group and OSI Pharmaceuticals.

Ball-and-stick model of erlotinib

The FDA also approved a label expansion for erlotinib, adding patients who have not previously received treatment for their metastatic NSCLC and whose tumors have either a deletion in exon 19  or exon 21 (L858R) substitution mutations in the EGFR gene as detected by the cobas EGFR mutation test. The mutation test is marketed by Roche Molecular Systems, a part of the Roche Group.

Erlotinib is already approved in the United States for treatment of locally advanced or metastatic NSCLC that progressed after initial treatment with a chemotherapy agent. The drug is also approved as a maintenance therapy for locally advanced or metastatic NSCLC patients who have not progressed after first-line treatment with a platinum-based chemotherapy.

The new first-line indication is based on the phase III European Randomized Trial of Tarceva Versus Chemotherapy (EURTAC) study. Treatment with 150 mg of erlotinib daily was compared to treatment with platinum-based chemotherapy in 174 patients. The progression-free survival was 10.4 months in the erlotinib group compared to 5.2 months in the chemotherapy group (P < .001, hazard ratio = 0.34).

The adverse events in the erlotinib arm that occurred in 30% or more of the patients included cough, shortness of breath, decreased appetite, diarrhea, rash, and weakness. More patients in the chemotherapy arm had severe grade 3/4 side effects compared to those in the erlotinib arm-20% (16 patients) and 6% (5 patients), respectively. The types and frequencies of adverse events were similar to those reported in previous NSCLC erlotinib clinical trials. Results from the open-label trial were originally published in Lancet Oncology in 2012.

The EGFR mutation test is manufactured by Roche and was used in the EURTAC trial to confirm patients’ EGFR mutation status.

About 10% of NSCLC patients have tumors with a mutation in the EGFR gene, approximately 43% of the EGFR mutations in NSCLC are exon 21 (L858R) mutations and 48% have a deletion of exon 19. Previous studies have shown patients with metastatic NSCLC cancer are sensitive to EGFR tyroskine kinase inhibitors such as erlotinib and gefitinib (Iressa), another oral EGFR inhibitor, if the patients’ tumors harbor specific EGFR mutations. Testing for EGFR mutations is not yet routine, although clinicians are advocating for molecular testing of all NSCLC patients, as several other targeted therapies, including crizotinib for ALK-mutated NSCLC cancer are also available in the United States.

Erlotinib is currently the only drug approved in the United States for EGFR-mutated NSCLC. Gefitinib was originally approved for second- and third-line treatment of NSCLC by the FDA in 2003 as part of an accelerated approval process based on a tumor response rate-a surrogate endpoint. The FDA withdrew the approval of the drug in 2012 after post-marketing studies failed to show an overall survival benefit of patients taking gefitinib. The drug is still used to treat NSCLC in other parts of the world, including Europe.

Another oral EGFR inhibitor, afatinib, has granted a priority review by the FDA in January of this year. The LUX-Lung clinical trials, including the LUX-Lung 3 trial showed afatinib improved progression-free survival of NSCLC patients when compared with chemotherapy. Afatinib, developed by Boehringer Ingelheim, also has a companion diagnostic being developed in parallel.