Concomitant echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase rearrangement and epidermal growth factor receptor mutation in non-small cell lung cancer patients from eastern India

J Cancer Res Ther. 2020 Jul-Sep;16(4):850-854. doi: 10.4103/jcrt.JCRT_678_18.

Abstract

Background: In non-small cell lung cancer common driver mutations such as epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) are usually mutually exclusive. This study aimed to elucidate the concurrence of EGFR mutation and ALK rearrangement in eastern India patients with primary lung adenocarcinoma and assess the response of EGFR tyrosine kinase inhibitor (TKI) therapy after 6 months in primary lung adenocarcinoma.

Methods: We retrospectively analyzed 198 adenocarcinomas for EGFR and ALK mutations. EGFR and ALK tests were done by real-time polymerase chain reaction and immunohistochemistry (IHC) techniques, respectively. Radiological response was assessed by Response Evaluation Criteria in Solid Tumors (version 1.1).

Results: EGFR/ALK co-alteration was found in 4 adenocarcinoma patients. All were males with advanced disease. Younger patients had exon 19 deletion whereas older ones showed exon 21 mutation. The initial option of ALK-TKI in all four patients was excluded straightaway due to the high-cost burden of ALK-TKI. Two of them showed a partial response while other two had stable disease after 6 months of EGFR TKI therapy.

Conclusion: EGFR/ALK co-alterations in adenocarcinomas albeit rare do exist. The challenge of monetary hurdle in developing countries with ALK TKI therapy can be handled by giving only EGFR TKI in these cases of concomitant mutations. Future perspective in research could be finding an agent with the potential of dual inhibition of ALK and EGFR.

Keywords: Adenocarcinoma; anaplastic lymphoma kinase; concomitant epidermal growth factor receptor anaplastic lymphoma kinase; epidermal growth factor receptor; lung.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / therapy
  • ErbB Receptors / genetics
  • Gene Rearrangement*
  • Humans
  • India
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy
  • Male
  • Middle Aged
  • Molecular Targeted Therapy / methods
  • Mutation*
  • Oncogene Proteins, Fusion / genetics*
  • Protein Kinase Inhibitors / therapeutic use
  • Protein-Tyrosine Kinases / genetics*
  • Retrospective Studies

Substances

  • EML4-ALK fusion protein, human
  • Oncogene Proteins, Fusion
  • Protein Kinase Inhibitors
  • EGFR protein, human
  • ErbB Receptors
  • Protein-Tyrosine Kinases