Cancer Res Treat.  2019 Jan;51(1):408-412. 10.4143/crt.2018.138.

Rare Mechanism of Acquired Resistance to Osimertinib in Korean Patients with EGFR-mutated Non-small Cell Lung Cancer

Affiliations
  • 1Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. silkahn@skku.edu
  • 2Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.
  • 3Department of Health Science and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Korea.
  • 4Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Seoul, Korea.

Abstract

Epidermal growth factor receptor (EGFR)"’tyrosine kinase inhibitors (TKIs) are effective clinical therapeutics for EGFR-mutant non-small cell lung cancer (NSCLC). Osimertinib, a thirdgeneration EGFR TKI, has proven effective against T790M mutations. However, the vast majority of patients acquire resistance following successful treatment. A 59-year-old female patient with metastatic NSCLC developed resistance after 43 weeks of osimertinib. CancerSCAN of the metastatic liver lesion revealed a EGFR C797G mutation at an allele frequency of 72%, a preexisting T790M mutation (73%) in cis and an exon 19 deletion (87%). Another 53-year-old female patient developed systemic progression after 10 months of osimertinib. CancerSCAN of the lung biopsy identified an EGFR L718Q mutation at an allele frequency of 7%, concomitant PIK3CA E545K (12.90%) and preexisting EGFR L858R (38%), but loss of the T790M mutation. The heterogeneity of osimertinib resistance mechanisms warrants further investigation into novel or combination agents to overcome the rare acquired resistances.

Keyword

Osimertinib; AZD9291; Resistance

MeSH Terms

Biopsy
Carcinoma, Non-Small-Cell Lung*
Exons
Female
Gene Frequency
Humans
Liver
Lung
Middle Aged
Phosphotransferases
Population Characteristics
Receptor, Epidermal Growth Factor
Phosphotransferases
Receptor, Epidermal Growth Factor
Full Text Links
  • CRT
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
    DB Error: unknown error