Gilotrif (afatinib) is an orally administered drug that is indicated as the first-line treatment for metastatic non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations. The drug was discovered and developed by Boehringer Ingelheim.
Boehringer Ingelheim received approval for Gilotrif from the US Food and Drug Administration (FDA) for the above indication in July 2013. The EGFR mutations that change the gene can be detected by using an FDA-approved test.
Boehringer Ingelheim submitted marketing authorisation application for Gilotrif in Europe in September 2012. The application is currently under review by the European Medical Agency (EMA).
Non-small-cell lung cancer disease details
Non-small-cell lung carcinoma (NSCLC) is a common type of lung cancer which spreads and develops slower than small-cell lung cancer.
The common symptoms of the disease include cough, chest pain, coughing up blood, weight and appetite loss, and shortness of breath.
Lung cancer is the most leading cause of deaths worldwide. An estimated 1.6 million new cases of lung cancer are reported worldwide every year. NSCLC accounts for 85% of the lung cancer cases.
Gilotrif (afatinib) mechanism of action
Gilotrif contains tyrosine kinase inhibitor that restrains many tyrosine kinase enzymes that are responsible for the activation of cancerous cells. The drug works by blocking the proteins that cause the cancerous cells to grow. The drug is available for oral administration.
Clinical trials of Gilotrif
Boehringer Ingelheim conducted phase II clinical trials on Gilotrif between December 2008 and May 2012. It was an open label, multi-centre, and single group assignment. It enrolled 70 subjects who were not previously exposed to chemotherapy for NSCLC.
Hycamtin is an anti-cancer drug developed by GlaxoSmithKline (GSK) as a treatment for relapsed small cell lung cancer (SCLC) in patients who have undergone and failed partial or complete first-line chemotherapy.
The primary outcome measure of the study was the objective response (CR, PR) as determined by the RECIST (Response Evaluation Criteria In Solid Tumors) criteria in 24 months. The secondary outcome measures included disease control, safety, pharmacokinetics, and presence of Kras and EGFR mutation.
The FDA approval for Gilotrif was based on phase III clinical trials known as LUX-Lung 3. The study enrolled 345 locally advanced or metastatic NSCLC patients who were EGFR mutation-positive. The patients were randomly administered either Gilotrif or up to six cycles of the chemotherapy drugs which included Pemetrexed and Cisplatin.
Results of the study showed that the patients treated with Gilotrif displayed a median progression-free survival (PFS) of 11.1 months when compared with 6.9 months in the chemotherapy arm. Among the 90% of patients who had the most common EGFR mutations in the study, the median PFS in Gilotrif arm was 13.6 months compared with 6.9 months in the chemotherapy arm. However, statistically significant difference was not found between Gilotrif and chemotherapy arms in terms of overall survival.
The common adverse events observed during the clinical trials relating to Gilotrif included diarrhoea, rashes, stomatitis, dry skin, paronychia, decreased appetite, and pruritus. Serious adverse events were found in about 29% of the Gilotrif-administered patients which included diarrhoea, vomiting, dyspnea, fatigue, and hypokalemia.
Boehringer company information
Boehringer Ingelheim is a leading international pharmaceutical company with its headquarters located in Ingelheim, Germany. The company engages in research, development, manufacturing and marketing of novel medications of high therapeutic value for human and veterinary medicine. It has more than 46,000 employees and operates about 140 affiliates worldwide.
Boehringer Ingelheim Pharmaceuticals is the US subsidiary of Boehringer Ingelheim Corporation which holds the marketing rights of Gilotrif in the US. The companion diagnostic test for genetic mutations ‘therascreen’ is marketed by Qiagen. Gilotrif will face competition from Xalkori, which is manufactured by Pfizer.