Priority Review Granted to Afatinib for EGFR+ Advanced NSCLC

The FDA has accepted a NDA for afatinib to treat patients with locally advanced or metastatic NSCLC who have tested positive for an EGFR mutation that has been identified through a companion diagnostic test.

The FDA has accepted a new drug application (NDA) for afatinib to treat patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who have tested positive for an epidermal growth factor receptor (EGFR) mutation that has been identified through a companion diagnostic test. The application was also granted priority review status by the FDA, meaning that the application will be given an expedited review process.

In addition to the NDA, in December the FDA granted afatinib orphan drug designation, which is granted to new therapeutic agents designed to treat diseases that affect fewer than 200,000 patients in the United States. If approved, afatinib would be the first drug on the market specifically available to treat patients with advanced or metastatic NSCLC who have an EGFR mutation.

Afatinib is a tyrosine kinase inhibitor (TKI) and an oral, irreversible ErbB family blocker that specifically inhibits EGFR (ErbB1), human epidermal receptor 2 (HER2 or ErbB2), and ErbB4. An overexpression of EGFR can lead to increased cell division in tumors. The drug is being investigated in several different clinical trials for patients who have been previously treated with TKI therapy and patients who are EGFR mutation-positive but have not yet received TKI therapy. Additionally, the drug is being investigated in metastatic breast cancer and head and neck cancer.

Boehringer Ingelheim Pharmaceuticals, the manufacturer of afatinib, filed the application after positive results were obtained through the phase III LUX-Lung 3 clinical trial. Results were presented at the 2012 American Society of Clinical Oncology (ASCO) meeting. The study found that patients who received afatinib had a median progression-free survival of 11.1 months compared with 6.9 months in patients who received a combination of pemetrexed (Alimta) and cisplatin chemotherapy (hazard ratio [HR] = 0.58; 95% CI, 0.43-0.78; P = .0004).1 Overall survival data is not yet available.

Afatinib may also work well in combination with cetuximab (Erbitux) for patients who have become resistant to treatment with erlotinib (Tarceva). A study presented at the 2012 European Society of Medical Oncology (ESMO) Congress found that the objective response rate in the first 60 evaluable patients enrolled in a study testing the combination was 30%.2

“The NDA filing of afatinib represents Boehringer Ingelheim’s commitment to addressing the significant need that exists for patients with EGFR mutation-positive advanced non-small cell lung cancer,” said Sabine Luik, MD, senior vice president, Medicine & Regulatory Affairs, and US Regional Medical Director for Boehringer Ingelheim Pharmaceuticals, Inc., in a statement. “We are pleased that the FDA has accepted the afatinib application under Priority Review and look forward to working with the agency in the coming months.”

Boehringer Ingelheim announced that the FDA target action date for the drug is scheduled for sometime in the third quarter of 2013.

In addition to the drug, a companion diagnostic test is also being developed by Boehringer Ingelheim and Qiagen, a company that develops diagnostic assays. Qiagen is developing the therascreen® EGFR RGQ PCR kit to identify patients with EGFR mutation-positive tumors.


  1. Yang JC-H, Schuler MH, Yamamoto N, et al. LUX-lung 3: a randomized, open-label, phase III study of afatinib versus pemetrexed and cisplatin as first-line treatment for patients with advanced adenocarcinoma of the lung harboring EGFR-activating mutations. J Clin Oncol. 2012;30(suppl; abstr LBA7500).
  2. Janjigian YY, Smit EF, Horn L, et al. Activity of afatinib/cetuximab in patients (pts) with EGFR mutant non-small cell lung cancer (NSCLC) and acquired resistance (AR) to EGFR inhibitors. Presented at: 37th European Society of Medical Oncology 2012 Congress; September 28 — October 2, 2012; Vienna, Austria. Abstract 1227.