Afatinib receives broadened approval for NSCLC

January 2018

The Food and Drug Administration (FDA) has granted approval for broadened use of afatinib (Gilotrif, Boehringer Ingelheim Pharmaceuticals) in first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC), whose tumors have non-resistant mutations in the epidermal growth factor receptor (EGFR).  The appropriate mutations in EGFR must be identified in laboratories using an FDA-approved testing method.  FDA approval of the drug was based on studies that demonstrated a durable response in a subset of 32 afatinib-treated patients with metastatic NSCLC’s who had non-resistant EGFR mutations (including S768I, L861Q and/or G719X), but not including NSCLC patients who had EGFR exon 19 deletions, or exon 21 L858R substitutions. The “non-resistant” mutations in EGFR were identified in laboratory tests in which afatinib inhibited growth in EGFR-mutant cell lines at clinically relevant doses of the drug. 
Three clinical trials showed patients with these mutations had durable responses when treated with afatinib (LUX-Lung 2 [NCT00525148], LUX-Lung 3 [NCT00949650], and LUX-Lung 6 [NCT01121393]). The overall response rate as assessed by independent radiology review was 66%.  Among the 21 responders, the proportion of patients with response duration of greater than or equal to 12 months was 52%, and the proportion of patients with response durations of greater than or equal to 18 months was 33%.
The original FDA approval for afatinib occurred in 2013 for the treatment of patients with metastatic NSCLC whose tumors had EGFR exon 19 deletions or exon 21 (L858R) substitutions, and in 2016 for metastatic squamous NSCLC that progressed after platinum-based chemotherapy. This 2018 FDA approval of afatinib represents a broadening of the subset of patients who can benefit from treatment with the drug.