Rare Mechanism of Acquired Resistance to Osimertinib in Korean Patients with EGFR-mutated Non-small Cell Lung Cancer.
- Author:
Jiyun LEE
1
;
Joon Ho SHIM
;
Woong Yang PARK
;
Hee Kyung KIM
;
Jong Mu SUN
;
Se Hoon LEE
;
Jin Seok AHN
;
Keunchil PARK
;
Myung Ju AHN
Author Information
- Publication Type:Case Report
- Keywords: Osimertinib; AZD9291; Resistance
- MeSH: Biopsy; Carcinoma, Non-Small-Cell Lung*; Exons; Female; Gene Frequency; Humans; Liver; Lung; Middle Aged; Phosphotransferases; Population Characteristics; Receptor, Epidermal Growth Factor
- From:Cancer Research and Treatment 2019;51(1):408-412
- CountryRepublic of Korea
- Language:English
- 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.
