FDA Approves Afatinib for Late-stage Lung Cancer

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On July 12, 2013, the FDA approved the tyrosine kinase inhibitor afatinib (Gilotrif) for the first-line treatment of patients with metastatic non–small cell lung cancer (NSCLC) whose tumors express epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test. Concurrent with this action, the FDA approved the therascreen EGFR RGQ PCR Kit for detection of EGFR exon 19 deletions or exon 21 (L858R) substitution mutations.

Study Details

The approval of afatinib was based on the demonstration of improved progression-free survival in a multicenter, international phase III trial (LUX-Lung 3). The trial enrolled 345 patients with metastatic NSCLC whose tumors tested positive for EGFR mutations. Patients were randomly assigned (2:1) to receive oral afatinib 40 mg once daily (n = 230) or pemetrexed (Alimta) plus cisplatin (n = 115). Randomization was stratified according to EGFR mutation status and race (Asian vs non-Asian). The major efficacy outcome was progression-free survival as assessed by an independent review committee.


A statistically significant improvement in progression-free survival was demonstrated for patients in the afatinib arm (P < .001). The median progression-free survival was 11.1 months in the afatinib arm and 6.9 months in the pemetrexed arm. In patients whose tumors had exon 19 deletions or exon 21 (L858R) substitution mutations, the median progression-free survival was 13.6 months in the afatinib arm and 6.9 months in the chemotherapy arm.

Objective response rates were 50.4% and 19.1% in the afatinib and chemotherapy arms, respectively. No statistically significant difference in overall survival between the two arms was demonstrated.

The most frequent adverse reactions from afatinib were diarrhea, rash/dermatitis acneiform, stomatitis, paronychia, dry skin, decreased appetite, and pruritus. Serious side effects included diarrhea that can result in kidney failure and severe dehydration, severe rash, lung inflammation and liver toxicity. 

Companion Diagnostic Test

The FDA’s approval of the therascreen EGFR RGQ PCR Kit is based on data from the clinical study used to support afatinib’s approval. Tumor samples from NSCLC participants in the clinical trial helped to validate the test’s use for detecting EGFR mutations in this patient population. ■