Heterogeneity among tumors with acquired resistance to EGFR tyrosine kinase inhibitors harboring EGFR ‐T790M mutation in non‐small cell lung cancer cells

Mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) gene respond well to treatment with EGFR tyrosine kinase inhibitors (EGFR-TKIs) including gefitinib and erlotinib in non-small cell lung cancer (NSCLC). Detection of these mutations has an important role for therapeutic decision-making in NSCLC treatment. However, all patients who experienced marked improvements with these drugs eventually developed disease progression after 10-20 months of treatment due to the acquisition of drug resistance. Approximately half of the cases with acquired resistance to EGFR-TKIs can be accounted for by a second-site mutation in exon 20 of the EGFR kinase domain T790M. In this study, 40 patients with advanced NSCLC who developed acquired resistance to EGFR-TKIs were selected. The diagnosis was defined based on the Jackman criteria for acquired resistance to EGFR-TKIs in lung cancers. Re-biopsy were performed at National cancer hospital and Oncology hospitals at Ha Noi and Ho Chi Minh City. Scorpion ARMS method was used to detect EGFR mutation status. In all, 40% (16/40) of the patients carried T790M mutation after the failure of EGFR-TKIs. The study demonstrated a critical role of molecular diagnostics for TKI acquired resistance through re-biopsies at the time of disease progression.

Download Full-text

P8‐21: Heterogeneity among tumors with acquired resistance to EGFR‐TKIs harboring EGFR‐T790M mutation in non‐small cell lung cancer cells

Respirology ◽

10.1111/resp.14150_533 ◽

2021 ◽

Vol 26 (S3) ◽

pp. 295-295

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cancer Cells ◽

Cell Lung Cancer ◽

Acquired Resistance ◽

Small Cell ◽

Small Cell Lung ◽

T790m Mutation ◽

Egfr T790m ◽

Egfr Tkis

Download Full-text

Genomic landscape of acquired resistance to third‐generation EGFR tyrosine kinase inhibitors in EGFR T790M‐mutant non–small cell lung cancer

Cancer ◽

10.1002/cncr.32809 ◽

2020 ◽

Vol 126 (11) ◽

pp. 2704-2712 ◽

Cited By ~ 1

Author(s):

Jiyun Lee ◽

Hong Sook Kim ◽

Boram Lee ◽

Hee Kyung Kim ◽

Jong‐Mu Sun ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Kinase Inhibitors ◽

Acquired Resistance ◽

Small Cell ◽

Third Generation ◽

Small Cell Lung ◽

Genomic Landscape ◽

Egfr Tyrosine Kinase Inhibitors ◽

Egfr T790m

Download Full-text

Real-world osimertinib for EGFR mutation-positive non-small-cell lung cancer with acquired T790M mutation

Future Oncology ◽

10.2217/fon-2020-0203 ◽

2020 ◽

Vol 16 (21) ◽

pp. 1537-1547

Author(s):

Fumio Imamura ◽

Madoka Kimura ◽

Yukihiro Yano ◽

Masahide Mori ◽

Hidekazu Suzuki ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Kinase Inhibitors ◽

Egfr Mutation ◽

Acquired Resistance ◽

Small Cell ◽

Small Cell Lung ◽

T790m Mutation ◽

Clinical Trial Registration

Aim: Osimertinib is a key drug for EGFR mutation-positive non-small-cell lung cancer (NSCLC). As the hazards ratio of overall survival in comparison with first-generation EGFR-tyrosine kinase inhibitors was almost similar between FLAURA and ARCHER 1050, salvage use of osimertinib is still a treatment option. Patients & methods: We retrospectively analyzed the clinical courses of EGFR mutation-positive NSCLC patients who were potential candidates for salvage osimertinib. Results: Among 524 patients enrolled from five hospitals, 302 patients underwent biopsy, with 52.6% detection rate of T790M. Osimertinib was administered in 93.6% of the T790M-positive patients. The overall response rate and median progression-free survival time of osimertinib were calculated with 147 patients, to be 55.6% and 17.2 months, respectively. Conclusion: Osimertinib is active for T790M-driven acquired resistance in EGFR-mutant NSCLC, but the detection of T790M was unsatisfactory. Clinical Trial Registration: UMIN000028989 (UMIN Clinical Trials Registry)

Download Full-text