FDA Grants Priority Review for EGFR-Mutant Lung Cancer Drug Afatinib


A promising new drug for a subtype of non-small cell lung cancer (NSCLC) was recently granted priority review status by the U.S. Food and Drug Administration (FDA). If approved, afatinib would be the first drug on the market specifically for treating advanced or metastatic NSCLC associated with epidermal growth factor receptor (EGFR) mutations.

Cancer cells often overexpress EGFR on their surfaces. These tyrosine kinase receptor proteins bind growth factors that stimulate cell growth and can lead to uncontrolled cell division and proliferation. Taken orally, afatinib inhibits EGFR and related receptors in the ErbB protein family. Unlike other tyrosine kinase blockers, however, afatinib’s effects are irreversible, meaning its activity should theoretically not decrease over time. This may make afatinib suitable for patients who have developed resistance—often associated with an EGFR-mutation subtype in exon 20—to other drugs like erlonitib (Tarceva).

A study on the effect of afatinib in cases of acquired resistance was presented at the 2012 European Society of Medical Oncology Congress. Treatment with afatinib plus cetuximab, a combination that had been found to be potent in a mutant cancer mouse model, caused tumor shrinkage in 40% of patients, with 4.7 months of progression-free survival.

The encouraging results of the much larger, 345-patient LUX-Lung phase III trial prompted afatinib manufacturer Boehringer Ingelheim Pharmaceuticals to apply for new drug approval from the FDA. Previously untreated patients with advanced EGFR-mutant NSCLC taking afatinib lived progression-free significantly longer (11.1 months) than those taking the current chemotherapy gold standard treatment, a combination of pemetrexed and cisplatin (6.9 months). Additionally, in patients with the most common EGFR mutations (del19 and L858R), progression-free survival was even longer: 13.6 months. Fifty-six percent of patients receiving afatinib also saw tumor shrinkage. Afatinib treatment, however, was associated with diarrhea, rash, and nail infections. This study was presented at the 2012 American Society of Clinical Oncology meeting.

In addition to the priority review, the FDA has also designated afatinib as an orphan drug, because it is meant for the treatment of a disease that affects fewer than 200,000 people in the U.S. The decision for afatinib approval could come in the third quarter of 2013. Testing for the EGFR mutation, which is present in 10% to 15% of white and 30% to 40% of Asian NSCLC patients, will be done with an associated diagnostic called TheraScreen, jointly developed by Boehringer Ingelheim and Qiagen. Afatinib is currently also in clinical development for use in breast and head and neck cancers.