Pooled Analysis Shows Activity of Afatinib Differs in NSCLC According to Uncommon EGFR Mutations
In a pooled analysis of the LUX-Lung 2, 3, and 6 trials reported in The Lancet Oncology, Yang et al found that the activity of afatinib (Gilotrif) differed according to uncommon EGFR mutations in advanced non–small cell lung cancer (NSCLC). Most patients with EGFR-mutant NSCLC have deletion mutations in exon 19 or Leu858Arg point mutations in exon 21 or both; approximately 10% have other mutations.
Mutations and Benefit
Among 600 patients receiving afatinib included in the analysis, 75 (12%) had uncommon EGFR mutations. Among 38 with point mutations or duplications in exons 18 to 21, 27 (71.1%) had objective response, median progression-free survival was 10.7 months, and median overall survival was 19.4 months. Among 14 patients with de novo Thr790Met mutations in exon 20 alone or in combination with other mutations, 2 (14.3%) had objective response, median progression-free survival was 2.9 months, and median overall survival was 14.9 months. Among 23 patients with exon 20 insertions, 2 (8.7%) had objective response, median progression-free survival was 2.7 months, and median overall survival was 9.2 months.
For patients with the most common of these mutations, objective response occurred in 14 (77.8%) of 18 with Gly719Xaa, 9 (56.3%) of 16 with Leu861Gln, and 8 (100%) of 8 with Ser768Ile.
The investigators concluded: “Afatinib was active in non-small-cell lung cancer tumours that harboured certain types of uncommon EGFR mutations, especially Gly719Xaa, Leu861Gln, and Ser768Ile, but less active in other mutations types. Clinical benefit was lower in patients with de-novo Thr790Met and exon 20 insertion mutations. These data could help inform clinical decisions for patients with non-small-cell lung cancer harbouring uncommon EGFR mutations.”
Yi-Long Wu, MD, of Guangdong Academy of Medical Sciences, is the corresponding author for The Lancet Oncology article. James C-H Yang, MD, of National Taiwan University, and Lecia V. Sequist, MD, of Massachusetts General Hospital Cancer Center, contributed equally to the article.
The study was funded by Boehringer Ingelheim. For full disclosures of the study authors, visit www.thelancet.com.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
