FDA Expands Approval of EGFR Inhibitor for Lung Cancer Treatment

January 17, 2018

The FDA has expanded the approval of afatinib (Gilotrif) to include the first-line treatment of metastatic non–small-cell lung cancer patients whose tumors have non-resistant EGFR mutations, including three newly identified substitution mutations.

The US Food and Drug Administration (FDA) has expanded the approval of the oral agent afatinib (Gilotrif) to include the first-line treatment of metastatic non–small-cell lung cancer (NSCLC) patients whose tumors have non-resistant epidermal growth factor receptor (EGFR) mutations. The new indication includes three additional non-resistant EGFR mutations: L861Q, G719X, and S768I. 

The FDA initially approved afatinib in 2013 for treating metastatic NSCLC patients whose tumors have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations, and in 2016 for patients with metastatic, squamous NSCLC whose disease has progressed after treatment with platinum-based chemotherapy.

“Compared with other EGFR mutations, L861Q, G719X, or S768I substitution mutations are associated with a poorer prognosis and limited treatment options,” said Edward Kim, MD, of the Levine Cancer Institute, Carolinas HealthCare System, in a press release. “The approval of Gilotrif as a targeted therapy for these additional non-resistant EGFR mutations significantly alters the treatment strategy for this population.”

The new approval was based on the pooled results of three clinical trials (LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6). Durable responses were seen with afatinib treatment in a subset of 32 metastatic NSCLC patients whose tumors carried S768I, L861Q, and/or G719X mutations. EGFR mutations were identified using the therascreen EGFR RGQ PCR Kit or Sanger sequencing.

The overall response rate among these patients was 66% (95% CI 47%–81%), with 21 patients responding. Among these, 52% had responses of 12 months or longer and 33% had responses of 18 months or longer.

The most common adverse events-occurring in 20% or more afatinib-treated patients-included decreased appetite, diarrhea, dry skin, nausea, paronychia, pruritus, rash/acneiform dermatitis, stomatitis, and vomiting.

The recommended afatinib dose is 40 mg once daily.