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

• Lee J
• Shim JH
• Park WY
• Kim HK
• Sun JM
• Lee SH
• Ahn JS
• Park K
• Ahn MJ

• KMID: 2437631
• DOI: http://doi.org/10.4143/crt.2018.138

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

Figure

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  Fig. 1. Acquired epidermal growth factor receptor (EGFR) C797G mutation. (A) Computed tomography of the liver demonstrates the tumor at baseline before osimertinib treatment (left), at partial response (middle), and during progression (right) after treatment with osimertinib. (B) The browser view reveals the mutational status of the tumor at baseline (top) and after osimertinib therapy (bottom). (C) Plot depicting EGFR (15.0) copy number amplification upon treatment with osimertinib.

• 

  Fig. 2. Acquired epidermal growth factor receptor (EGFR) L718Q mutation. (A) Computed tomography of the chest showed the tumor at baseline before osimertinib treatment (left), at partial response (middle), and during disease progression (right) after treatment with osimertinib. (B) The browser view reveals the mutational status of the tumor at baseline (top) and after osimertinib therapy (bottom).

Reference

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