July 18, 2013 – The U.S. Food and Drug Administration (FDA) very recently approved Gilotrif (afatinib) for patients with late stage (metastatic) non-small cell lung cancer (NSCLC) whose tumors express specific types of epidermal growth factor receptor (EGFR) gene mutations, as detected by an FDA-approved test.
Lung cancer is the leading cause of cancer-related death among men and women. According to the National Cancer Institute, an estimated 228,190 Americans will be diagnosed with lung cancer, and 159,480 will die from the disease this year. About 85 percent of lung cancers are NSCLC, making it the most common type of lung cancer. EGFR gene mutations are present in about 10 percent of NSCLC, with the majority of these gene mutations expressing EGFR exon 19 deletions or exon 21 L858R substitution.
Gilotrif is a tyrosine kinase inhibitor that blocks proteins that promote the development of cancerous cells. It is intended for patients whose tumors express the EGFR exon 19 deletions or exon 21 L858R substitution gene mutations. Gilotrif is being approved concurrently with the therascreen EGFR RGQ PCR Kit, a companion diagnostic that helps determine if a patient’s lung cancer cells express the EGFR mutations.
“Today’s approvals further illustrate how a greater understanding of the underlying molecular pathways of a disease can lead to the development of targeted treatments,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Gilotrif is the second drug approved this year for patients with untreated metastatic NSCLC whose tumors have the EGFR exon 19 deletions or exon 21 L858R substitution mutations.”
In May, the FDA approved Tarceva (erlotinib) for first-line treatment of patients with NSCLC. Tarceva’s new indication was approved concurrently with the cobas EGFR Mutation Test, a companion diagnostic to identify patients with tumors having the EGFR gene mutations.
“The approval of companion diagnostic tests and drugs are important developments in oncology, as they help us bring safe and effective treatments to patients who need them,” 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.
The FDA’s approval of the therascreen EGFR RGQ PCR Kit is based on data from the clinical study used to support Gilotrif’s approval. Tumor samples from NSCLC participants in the clinical trial helped to validate the test’s use for detecting EGFR mutations in this patient population.
Gilotrif’s safety and effectiveness were established in a clinical study of 345 participants with metastatic NSCLC whose tumors harbored EGFR mutations. Participants were randomly assigned to receive Gilotrif or up to six cycles of the chemotherapy drugs pemetrexed and cisplatin.
Participants receiving Gilotrif had a delay in tumor growth (progression-free survival) that was 4.2 months later than those receiving chemotherapy. There was no statistically significant difference in overall survival.
Common side effects of Gilotrif include diarrhea, skin breakouts that resemble acne, dry skin, itching (pruritus), inflammation of the mouth, skin infection around the nails (paronychia), decreased appetite, decreased weight, inflammation of the bladder (cystitis), nose bleed, runny nose, fever, eye inflammation and low potassium levels in the blood (hypokalemia). Serious side effects include diarrhea that can result in kidney failure and severe dehydration, severe rash, lung inflammation and liver toxicity.
The FDA reviewed Gilotrif under its priority review program, which provides an expedited review for drugs that may provide safe and effective therapy when no satisfactory alternative therapy exists, or offer significant improvement compared to marketed products.
Gilotrif is marketed by Ridgefield, Conn.-based Boehringer Ingelheim Pharmaceuticals, Inc. The therascreen EGFR RGQ PCR Kit is manufactured by QIAGEN Manchester Ltd., based in the United Kingdom. The cobas EGFR Mutation Test is manufactured by the Roche Molecular Systems in Pleasanton, Calif., and Tarceva is co-marketed by California-based Genentech, a member of the Roche Group, and OSI Pharmaceuticals of Farmingdale, N.Y.
For more information:
FDA: Office of Hematology and Oncology Products
FDA: CDRH Office of In Vitro Diagnostics and Radiological Health
FDA: Approved Drugs: Questions and Answers
FDA: Drug Innovation
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.