Clinical Activity of Afatinib in Patients With Non-Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations: A Spanish Retrospective Multicenter Study

Clin Lung Cancer. 2020 Sep;21(5):428-436.e2. doi: 10.1016/j.cllc.2020.04.011. Epub 2020 Apr 25.


Introduction: Uncommon epidermal growth factor receptor (EGFR) mutations (u-EGFRm) are a heterogeneous group of molecular alterations and have also been reported as comutations with other EGFR mutations (complex mutations) in non-small-cell lung cancer (NSCLC). Afatinib has shown activity against some u-EGFRm, and we examined its efficacy in Spanish clinical practice.

Patients and methods: Data of 67 patients with advanced NSCLC with u-EGFRm treated with afatinib between 2012 and 2017 at 23 Spanish institutions were reviewed. u-EGFRm were analyzed as complex mutations (group A), EGFR exon 20 insertions (ins20; group B), or single mutations (group C). Efficacy was evaluated in terms of overall survival (OS) and tumor response.

Results: Group A complex u-EGFRm consisted of double mutations of G719X+E709F, G719X+S768I, G719X+L861Q, L858R+T790M, L858R+S768I, L858R+S765I, del19+S768I, del19+L747S, or R776C+L861Q. No differences in clinical characteristics were found between groups A (n = 20), B (n = 23), and C (n = 24). Afatinib was administered as first-line therapy in 80% of patients. Median time of receipt of therapy was 4.2 months (range, 2.0-12.9 months). Median OS for the entire cohort was 19.9 months (95% confidence interval, 9.7, 30.1). Hazard ratios for OS were 0.26 (95% confidence interval, 0.10, 0.71; P = .008) and 0.40 (95% confidence interval, 0.17, 0.95; P = .037) for groups A and C compared to B, respectively. Response was significantly higher in groups A (70%) and C (54%) compared to B (13%; pairwise comparison P < .001 and .008, respectively).

Conclusion: In clinical practice, afatinib was active in patients with u-EGFRm NSCLC, particularly in complex and single mutations. Further strategies are needed for patients with ins20, a subgroup u-EGFRm with a lower clinical benefit with afatinib.

Keywords: Afatinib; EGFR mutations; NSCLC; Retrospective; Uncommon.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Afatinib / therapeutic use*
  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • ErbB Receptors / genetics
  • Female
  • Follow-Up Studies
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Mutation*
  • Prognosis
  • Protein Kinase Inhibitors / therapeutic use*
  • Retrospective Studies
  • Spain
  • Survival Rate


  • Protein Kinase Inhibitors
  • Afatinib
  • EGFR protein, human
  • ErbB Receptors