Durable complete response after afatinib and crizotinib in an advanced non-small cell lung cancer patient with EGFR L861Q mutation and acquired MET amplification: a case report

Ann Palliat Med. 2020 Sep;9(5):3609-3613. doi: 10.21037/apm-19-482. Epub 2020 Jun 29.


Epidermal growth factor receptor (EGFR) L861Q mutation is a non-classical mutation, with a low incidence, poor response, and uncertain resistance mechanisms when treated by an EGFR tyrosine kinase inhibitor (EGFR-TKI). The liver is one of the most common distant organs to metastasize in nonsmall cell lung cancer (NSCLC), and achieving complete remission treatment for the liver is difficult. In this report, a patient was diagnosed with advanced lung adenocarcinoma harboring the EGFR L861Q mutation and responded well to afatinib for 16 months. Complete response and partial response (PR) appeared in the liver metastasis and primary lesion respectively. Following this, afatinib plus crizotinib overcame the acquired resistance of MET amplification and brought about the complete remission of the liver for 10 months. Interestingly, the liver remission endured for 22 months and persisted even when the disease progressed and the EGFR T790M mutation emerged. To our knowledge, this is the first time that afatinib induced longterm liver remission in a patient with an EGFR non-classical mutation, and in whom crizotinib with afatinib proved to be a reliable treatment for overcoming MET amplification resistance with an EGFR non-classical mutation. This precise and individualized gene-based treatment significantly prolonged the survival time of this stage IV case with brain metastases yielding 26 months of progression-free survival (PFS) time and more than 3 years of overall survival time.

Keywords: EGFR L861Q mutation; EGFR T790M mutation; MET amplification; Non-small cell lung cancer (NSCLC); case report; liver metastasis.

Publication types

  • Case Reports

MeSH terms

  • Afatinib / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Crizotinib / therapeutic use*
  • Drug Resistance, Neoplasm / genetics
  • ErbB Receptors / genetics
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Mutation
  • Protein Kinase Inhibitors / therapeutic use


  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Afatinib
  • Crizotinib
  • EGFR protein, human
  • ErbB Receptors