[Resistance to anti-EGFR through the successive and cumulative acquisition of two new oncogenic addictions: BRAF and ALK]

Rev Mal Respir. 2024 Jun;41(6):451-454. doi: 10.1016/j.rmr.2024.05.003. Epub 2024 May 24.
[Article in French]

Abstract

Targeted therapies are the standard first-line treatment for metastatic lung adenocarcinoma with certain molecular abnormalities. These abnormalities are particularly common in Southeast Asia and French Polynesia. A 51-year-old Tahitian female non-smoker was diagnosed in 2018 with stage IV lung adenocarcinoma harboring a p.L858R EGFR mutation. She received gefitinib as first-line treatment. Due to locoregional progression and the presence of a resistance mutation (p.T790M of EFGR), she received osimertinib as second-line treatment, after which chemotherapy was proposed as 3rd-line treatment. An additional biopsy detected not only the previously known EGFR mutation, but also a BRAF p.V600E mutation. Following disease progression during chemotherapy, the patient received targeted therapies combining dabrafenib, trametinib and osimertinib. Due to a dissociated response after four months of treatment, a 5th line of paclitaxel bevacizumab was initiated. Subsequent to additional progression and given the ALK rearrangement shown on the re-biopsy, 6th-line treatment with alectinib was proposed. As the response was once again dissociated, a final line was proposed before stopping active treatments due to their toxicity and overall deterioration in the patient's state of health. This exceptional case is characterized by resistance to anti-EGFR through the successive and cumulative acquisition of two new oncogene addictions. The authors underline the importance of re-biopsy at each progression, leading (if at all feasible) to yet around round of targeted therapy.

Keywords: ALK; Addiction oncogénique; Adénocarcinome bronchique; BRAF; Bronchial adenocarcinoma; EGFR; Oncogenic addiction; Targeted therapies; Thérapies ciblées.

Publication types

  • Case Reports
  • English Abstract

MeSH terms

  • Acrylamides / pharmacology
  • Acrylamides / therapeutic use
  • Adenocarcinoma of Lung / drug therapy
  • Adenocarcinoma of Lung / genetics
  • Adenocarcinoma of Lung / pathology
  • Anaplastic Lymphoma Kinase / antagonists & inhibitors
  • Anaplastic Lymphoma Kinase / genetics
  • Aniline Compounds / pharmacology
  • Aniline Compounds / therapeutic use
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Drug Resistance, Neoplasm*
  • ErbB Receptors* / genetics
  • Female
  • Gefitinib / pharmacology
  • Gefitinib / therapeutic use
  • Humans
  • Indoles
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Middle Aged
  • Mutation
  • Oncogene Addiction*
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins B-raf / genetics
  • Pyrimidines

Substances

  • Acrylamides
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Aniline Compounds
  • Antineoplastic Agents
  • BRAF protein, human
  • EGFR protein, human
  • ErbB Receptors
  • Gefitinib
  • Indoles
  • osimertinib
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins B-raf
  • Pyrimidines