Abstract
The U.S. Food and Drug Administration approved afatinib for first-line treatment of metastatic non–small cell lung cancer in patients whose tumors have specific epidermal growth factor receptor mutations. The drug was approved along with the Therascreen EGFR RGQ PCR Kit companion diagnostic test.
The U.S. Food and Drug Administration approved afatinib (Gilotrif; Boehringer Ingelheim Pharmaceuticals) for first-line treatment of metastatic non–small cell lung cancer (NSCLC) in patients whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions and exon 21 L858R substitution mutations. The drug was approved along with the Therascreen EGFR RGQ PCR Kit (Qiagen), a companion diagnostic test to detect those mutations.
Afatinib is an oral tyrosine kinase inhibitor (TKI) that irreversibly binds to EGFR, HER2, and HER4. The covalent attachment to EGFR distinguishes the more potent afatinib from the reversible EGFR TKIs erlotinib (Tarceva; Roche and Astellas Pharma) and gefitinib (Iressa; AstraZeneca), the manufacturer says.
“This approval is another shining example of the identification of a molecular driver of disease in a specific subset of patients, and the development and matching of genotype-directed therapy to that appropriate patient subset,” comments Trever Bivona, MD, PhD, assistant professor of hematology and oncology at the University of California, San Francisco.
EGFR mutations occur in about 10% of NSCLC tumors. Afatinib targets roughly 90% of EGFR mutations found in NSCLC.
The drug's approval was based on results from the randomized phase III LUX-Lung 3 trial that compared the drug to the chemotherapy drug pemetrexed (Alimta; Lilly) plus cisplatin. First presented at the American Society of Clinical Oncology 2012 Annual Meeting and subsequently reported in the Journal of Clinical Oncology, the study included 345 patients with metastatic EGFR-mutant NSCLC who had not received previous chemotherapy.
Overall, median progression-free survival (PFS) reached 11.1 months for the afatinib arm and 6.9 months for the chemotherapy arm. For the 308 patients with exon 19 deletions and exon 21 L858R mutations, median PFS improved to 13.6 months with afatinib compared with 6.9 months with chemotherapy. A preliminary overall survival analysis didn't show a statistically significant difference between the groups; Bivona notes that one reason may be that 65% of patients receiving chemotherapy crossed over to receive an EGFR inhibitor. Side effects of afatinib are similar to other EGFR inhibitors and include diarrhea, rash, and stomatitis.
Clinicians in the United States now have two very good options—afatinib and erlotinib—for newly diagnosed patients with EGFR-mutant advanced NSCLC, comments Pasi Jänne, MD, PhD, director of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute in Boston, MA. “We won't know which is better to start patients with until a clinical trial evaluates them head-to-head,” he says.
Jänne also sees afatinib as a building block for new combination therapies. “I don't think any of us believe that a single drug is going to cure even the most sensitive lung cancer population,” he explains. “We now need to see if we can effectively combine treatments with afatinib.”
Afatinib is also being tested in head and neck cancer, breast cancer, gastric cancer, and esophageal cancer.
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