The tyrosine kinase inhibitor afatinib received Food and Drug Administration approval July 12 for the first-line treatment of metastatic non–small cell lung cancers that express epidermal growth factor exon 19 deletions or exon 21 L858R substitution gene mutations. Its brand name is Gilotrif, and it will be marketed by Boehringer Ingelheim.
The agency also approved a kit to detect those mutations, Qiagen’s therascreen EGFR RGQ PCR Kit; they occur in most of the 10% of non–small cell lung cancer (NSCLC) tumors that have epidermal growth factor receptor mutations.
Another kinase inhibitor, Genentech’s erlotinib (Tarceva), was approved for the same indication in May, along with its own mutation screening tool, Roche’s cobas EGFR Mutation Test.
In the study that won approval for afatinib, 230 NSCLC patients with the mutations were randomized to afatinib 40 mg orally; 115 others were randomized to up to six cycles of pemetrexed and cisplatin. Median progression-free survival was 11.1 months in the afatinib group and 6.9 months in the chemotherapy group. There was no statistically significant difference in overall survival. The therascreen kit was validated in that trial.
The side effects of Gilotrif include diarrhea, which can lead to kidney failure and severe dehydration; liver toxicity; lung inflammation; and severe rashes. Less serious side effects include acnelike skin eruptions, dry skin, pruritus, mouth inflammation, paronychia, decreased appetite, decreased weight, cystitis, nosebleed, runny nose, fever, eye inflammation, and hypokalemia.
In a phase II Japanese study published online by the Journal of Clinical Oncology July 1, 50 mg per day of afatinib demonstrated "modest but noteworthy efficacy" in NSCLC patients who progressed after being on erlotinib or gefitinib, or both, for 12 or more weeks.
Of 62 treated patients, 45 (72.6%) were EGFR mutation positive in their primary tumor; 51 (82.3%) patients had developed resistance to erlotinib or gefitinib. Median progression-free survival was 4.4 months and median overall survival 19.0 months (J. Clin. Oncol. 2013 July 1 [doi: 10.1200/JCO.2012.45.0981]).