Incidence of T790M in Patients With NSCLC Progressed to Gefitinib, Erlotinib, and Afatinib: A Study on Circulating Cell-free DNA

Autor: Mario Miccoli, Iacopo Petrini, Marzia Del Re, Antonio Chella, Marina Chiara Garassino, Giulia Gianfilippo, Daniele Pozzessere, Francesca Mazzoni, Stefania Crucitta, Giuliana Restante, Eleonora Rofi, Romano Danesi, Simona Valleggi
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
Oncology
Cancer Research
Lung Neoplasms
Afatinib
T790M
0302 clinical medicine
Carcinoma
Non-Small-Cell Lung
Antineoplastic Combined Chemotherapy Protocols
heterocyclic compounds
Epidermal growth factor receptor
biology
Incidence
Gefitinib
Middle Aged
Prognosis
ErbB Receptors
Survival Rate
030220 oncology & carcinogenesis
Disease Progression
Female
Erlotinib
Cell-Free Nucleic Acids
Tyrosine kinase
medicine.drug
Pulmonary and Respiratory Medicine
medicine.medical_specialty
EGFR
Erlotinib Hydrochloride
03 medical and health sciences
Internal medicine
medicine
Humans
Lung cancer
neoplasms
Aged
Retrospective Studies
Tyrosine kinase inhibitors
business.industry
medicine.disease
respiratory tract diseases
030104 developmental biology
Drug resistance
Non-squamous non-small cell lung cancer
Mutation
biology.protein
EGFR Activating Mutation
business
Follow-Up Studies
Zdroj: Clinical Lung Cancer. 21:232-237
ISSN: 1525-7304
DOI: 10.1016/j.cllc.2019.10.003
Popis: Background Insights into the mechanism of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) could provide important information for further patient management, including the choice of second-line treatment. The EGFR T790M mutation is the most common mechanism of resistance to first- and second-generation EGFR TKIs. Owing to its biologic relevance in the response of non–small-cell lung cancer (NSCLC) to the selective pressure of treatment, the present study investigated whether the occurrence of T790M at progression differed among patients receiving gefitinib, erlotinib, or afatinib. Patients and Methods The present retrospective study included patients with NSCLC with an EGFR activating mutation, who had received gefitinib, erlotinib, or afatinib as first-line treatment. Plasma samples for the analysis of cell-free DNA were taken at disease progression and analyzed using a digital droplet polymerase chain reaction EGFR mutation assay. Results A total of 83 patients were enrolled; 42 had received gefitinib or erlotinib and 41afatinib. The patient characteristics were comparable across the 2 groups. The median time to progression (TTP) was 14.4 months for the gefitinib and erlotinib group and 10.2 months for the afatinib group (P = .09). Of the 83 patients, 47 (56.6%) were positive for the T790M in plasma. A greater incidence of T790M was observed in patients with progression during gefitinib or erlotinib therapy compared with patients treated with afatinib (33 [79%] vs. 14 [34%], respectively; odds ratio, 7.1; 95% confidence interval, 2.7-18.5; P = .0001). Conclusions Although gefitinib, erlotinib, and afatinib showed a comparable TTP in patients receiving first-line therapy, the incidence of T790M differed among them, as demonstrated by the present study, which could have implications for the choice of second-line treatment.
Databáze: OpenAIRE
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