Patients with non small–cell lung cancer (NSCLC) may be successfully stratified to targeted therapy or chemotherapy depending on the complexity of their cancer’s EGFR mutations, according to research published in Cancer.1

Up to 15% of white patients and half of Asian patients with NSCLC have detectable EGFR mutations, which can lead to an 80% objective response rate (ORR) with EGFR–tyrosine kinase inhibitors (TKIs). While as many as 90% of these mutations are due to in-frame deletion in exon 19 (del-19) or a point mutation in exon 21 (21L858R), some patients have 2 or more EGFR mutations — cases classified as “complex.”

For this study, researchers evaluated whether different complex mutations lead to different clinical outcomes among patients treated with EGFR-TKIs. Of 16,840 patients screened, primary complex mutations were noted in 187, and 51 who received a first-line TKI were included in a survival analysis. The median patient age was 63 years and 25.5% were smokers.

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Patients were grouped by variety of complex mutation: del-19 plus 21L858R (group A, 15 patients), del-19 or 21L858R + an atypical mutation (group B, 16 patients), 2 atypical mutations (group C, 8 patients), and a primary drug resistance mutation (group D, 12 patients).

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An objective response (complete or partial) was noted in 75% of patients in group A, 60% of patients in group B, 71% of patients in group C, and 8.3% of patients in group D; the disease control rates were 100%, 86.7%, 85.7%, and 16.7%, respectively.

In groups A, B, C, and D, respectively, median progression-free survival was 18.2 months, 9.7 months, 9.6 months, and 1.4 months.

The authors concluded that “EGFR-TKI therapy is effective in patients with Del-19 + 121L858R mutations, Del-19/21L858R1 + atypical mutations, and double atypical mutations but is less effective in patients with a primary drug-resistant pattern.”


  1. Zhang B, Wang S, Qian J, et al. Complex epidermal growth factor receptor mutations and their responses to tyrosine kinase inhibitors in previously untreated advanced lung adenocarcinomas. Cancer. 2018 Mar 15. doi: 10.1002/cncr.31329 [Epub ahead of print]