Gilotrif Approved for Metastatic Lung Cancer with EGFR Mutations, Concurrent with a Companion Diagnostic Test

July 2013, Vol 4, No 6 - FDA Approvals, News & Updates


The US Food and Drug Admini­stration (FDA) approved the tyrosine kinase inhibitor afatinib (Gilotrif; Boehringer Ingelheim Pharmaceuti­cals) for the treatment of patients with metastatic non–small-cell lung cancer (NSCLC) who have the epidermal growth factor receptor (EGFR) gene mutations exon 19 deletions or exon 21 L858R substitution. The FDA approved afatinib under its priority review program, which offers an expedited review for drugs that provide safe and effective therapy when no good alternatives exist or for drugs that provide significant therapeutic improvement over available agents.

Afatinib was approved concurrently with a companion diagnostic, the thera­­screen EGFR RGQ PCR Kit (manufactured by QIAGEN, Manchester, United Kingdom), that identifies patients with the EGFR mutations. These types of mutations occur in approximately 10% of NSCLC tumors, and the majority of these mutations are either exon 19 deletions or exon 21 L858R substitution.

“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. “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 first agent, erlotinib (Tarceva), was approved in May for the first-line treatment of patients with NSCLC and was also concurrently approved with a companion diagnostic (the cobas EGFR Mutation Test).

Afatinib’s safety and efficacy were established in a clinical study of 345 patients with metastatic NSCLC plus EGFR mutations. Patients were randomized to afatinib or to chemotherapy with pemetrexed and cisplatin. Progression-free survival was 4.2 months longer in the group that received afatinib than in the chemotherapy group. No significant difference in overall survival was seen between the 2 treatment arms.

The common side effects reported with afatinib include diarrhea, skin breakouts that resemble acne, dry skin, pruritus, inflammation of the mouth, paronychia, decreased appetite and weight, cystitis, nose bleed, runny nose, fever, eye inflammation, and hypokalemia. Serious side effects include diarrhea that can result in kidney failure and severe dehydration, severe rash, lung inflammation, and liver toxicity.

The FDA’s approval of the thera­screen EGFR RGQ PCR Kit was based on data from the safety and efficacy clinical study that was used for the approval of afatinib. Tumor samples from patients with NSCLC plus mutations helped to validate the test’s benefit in detecting EGFR mutations in this patient population. (July 12, 2013)