The FDA has expanded the frontline indication for afatinib (Gilotrif) to include the treatment of patients with metastatic non–small cell lung cancer (NSCLC) whose tumors harbor uncommon EGFR alterations in L861Q, G719X, and/or S768I.
The approval for uncommon, non-resistance EGFR mutations was based on findings from 32 patients in the phase II LUX-Lung 2 trial (LL2) and the randomized phase III trials known as LUX-Lung 3 (LL3) and LUX-Lung 6 (LL6). The confirmed objective response rate (ORR) with afatinib in these patients was 66% (95% CI, 47%-81%). Of those responding, 52% had duration of response lasting ≥12 months and 33% had response duration of ≥18 months.
Afatinib was initially approved by the FDA in 2013 for the treatment of patients with metastatic NSCLC with exon 19 deletions or exon 21 L858R substitutions. In 2016, this indication was expanded to include patients with squamous histology following progression on a platinum-based chemotherapy.
“For our patients who have up until now had no proven options, we actually have an evidence-based treatment option in afatinib—in addition to chemotherapy—that I think will be a very valuable addition,” H. Jack West, MD, thoracic oncologist, Swedish Cancer Institute of Swedish Medical Center, told OncLive in an interview. “Over the last 2 years we have learned that EGFR mutation isn’t just a binary ‘yes or no, you have it.’ It’s more nuanced than that, and 88% to 90% of patients have 1 or 2 common EGFR mutations but that leaves 10% to 12% of our mutations in EGFR that are rare mutations.”
The overall frequency of patients with uncommon EGFRmutations was 18% in LL2 (n = 23), and 11% in both LL3 (n = 37) and LL6 (n = 40). A posthoc analysis examined 75 patients (13%) across the 3 trials who received afatinib and were positive for uncommon EGFR mutations, which included resistant alterations. The approval was specifically for those with nonresistant EGFR alterations, which were present in 32 patients in the trials.
“Historically, for these rare mutations, we might have been futile in giving one of the first-generation inhibitors, like erlotinib (Tarceva) or gefitinib (Iressa), which has not been particularly successful. But, afatinib has been studied better, and clearly does have some activity for the majority of these,” said West. “It does not work well for exon 20 insertions or T790M but for many of the other mutations that we do pick up we do now have an option with the approval of afatinib for these rare mutations.”