Dacomitinib overcomes acquired resistance to osimertinib in advanced NSCLC patients with EGFR L718Q mutation: A two-case report

Medicine (Baltimore). 2024 Jul 12;103(28):e38789. doi: 10.1097/MD.0000000000038789.

Abstract

Rationale: Acquired resistance still inevitably occurs in patients treated with third-generation TKI osimertinib. Although the EGFR L718Q mutation has been reported as a scarce mechanism of osimertinib resistance, advanced therapeutic strategies are still in development. In this report, we included 2 cases of patients who acquired EGFR L858R/L718Q mutation after osimertinib and were overcome by dacomitinib.

Patient concerns: Case 1: A 77-year-old woman was diagnosed with stage IV lung adenocarcinoma. Case 2: A 64-year-old woman was diagnosed with stage IV lung adenocarcinoma.

Diagnoses: Case 1: The patient was diagnosed with adenocarcinoma with EGFR L858R mutation. Since then, treatment with gefitinib was administrated, leading to a progression-free survival of 18 months. The treatment was switched to osimertinib based on the detection of EGFR T790M mutation, resulting in a progression-free survival of 24 months. Subsequently, EGFR L718Q mutation was detected. Case 2: The patient was diagnosed with adenocarcinoma with EGFR L858R mutation. Icotinib was used as the first-line treatment for 7 months. Osimertinib was applied as the second-line treatment for 13 months based on the EGFR T790M mutation. Subsequently, EGFR L718Q mutation was detected.

Interventions: Case 1: Dacomitinib was administered. Case 2: Dacomitinib was administered.

Outcomes: Case 1:The progression-free survival was 8 months. Case 2: The progression-free survival was 3 months.

Lessons: Dacomitinib is a potential treatment option for NSCLC patients with EGFR L718Q mutation after resistance to Osimertinib. Further research is needed to validate the efficacy of Dacomitinib in this context.

Publication types

  • Case Reports

MeSH terms

  • Acrylamides* / therapeutic use
  • Adenocarcinoma of Lung / drug therapy
  • Adenocarcinoma of Lung / genetics
  • Aged
  • Aniline Compounds* / therapeutic use
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Drug Resistance, Neoplasm* / genetics
  • ErbB Receptors* / genetics
  • Female
  • Humans
  • Indoles
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Middle Aged
  • Mutation*
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrimidines
  • Quinazolinones* / therapeutic use

Substances

  • osimertinib
  • Acrylamides
  • Aniline Compounds
  • ErbB Receptors
  • dacomitinib
  • Quinazolinones
  • EGFR protein, human
  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Indoles
  • Pyrimidines