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FDA Approves Afatinib for Metastatic NSCLC

Ben Leach
Published Online: Friday, July 12, 2013
Dr. Richard Pazdur

Richard Pazdur, MD

The FDA has approved the novel tyrosine kinase inhibitor afatinib (Gilotrif) for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) who express specific types of EGFR mutations. The agency also concurrently approved a companion diagnostic to identify patients with these particular mutations.

Afatinib is a pan-HER inhibitor that targets the entire ErbB/HER family of receptors, which includes epidermal growth factor receptor (EGFR, or ErbB1) and human epidermal growth factor receptor 2 (HER2, or ErbB2). Each of these tyrosine kinases is implicated in varying ways among different cancers, so the drug is being investigated in numerous tumor types, such as breast cancer and head and neck cancer in addition to lung cancer.

Approximately 10% of all cases of NSCLC have mutations of EGFR, and about 90% of these mutations express either an exon 19 deletion or an exon 21 L858R substitution. These specific mutations are targeted by afatinib, and so the therascreen EGFR RGQ PCR Kit has been approved as a companion diagnostic to identify them. Earlier this year, the FDA expanded the approval of erlotinib (Tarceva) to include this same group of patients, along with a companion diagnostic, the cobas EGFR Mutation Test.

“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, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, in a statement. “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.”

The agency based its afatinib approval on the results of the phase III LUX-Lung 3 trial, the results of which were first presented at the 2012 Annual Meeting of the American Society of Clinical Oncology (ASCO) and recently published in the Journal of Clinical Oncology. In that trial, 345 patients with stage IIIB/IV lung adenocarcinoma were randomly assigned to treatment with either afatinib or a combination of cisplatin and pemetrexed. The primary endpoint was progression-free survival (PFS).

The study found that patients in the afatinib arm of the study experienced a median PFS of 11.1 months compared with 6.9 months in the cisplatin and pemetrexed arm (hazard ratio [HR] = 0.58; 95% CI, 0.43-0.78; P = .001). The difference in survival was more pronounced in patients who expressed either an exon 19 deletion or an exon 21 L858R substitution. Patients with those specific mutations who received afatinib experienced a median PFS of 13.6 months compared with 6.9 months in the cisplatin and pemetrexed arm (HR = 0.47; 95% CI, 0.34-0.65; P = .001). The most common treatment-related adverse events experienced by patients in the study who received afatinib were diarrhea, rash or acne, and stomatitis.

According to the National Cancer Institute, lung cancer is the leading cause of cancer-related death among men and women, with an estimated 228,190 Americans expected to receive a diagnosis of the disease this year and another 159,480 dying from the disease.

Afatinib is marketed by Boehringer Ingelheim Pharmaceuticals, Inc., based on Ridgefield, Connecticut, and the therascreen EGFR RGQ PCR Kit is manufactured by QIAGEN Manchester Ltd. in the United Kingdom.


Sequist LV, Yang J C-H, Yamamoto N, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations [published online ahead of print July 1, 2013]. J Clin Oncol. doi: 10.1200/JCO.2012.44.2806.


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