The third generation epidermal growth gactor receptor-tyrosine Kinase Inhibitor(EGFR-TKI) osimertinib has obvious curative effect for EGFR sensitive mutation and T790M mutation(PMID 27959700), but acquired drug resistance will occur. Previous studies show that apoptosis escape can lead to EGFR-TKI resistance.Osimertinib resistant cells show abnormal activation of PI3K/AKT/BIM activation(PMID 28765329). The classical drug aspirin can effectively decrease AKT phosphorylation and activate of BIM(PMID 28881293).So Investigators speculate that aspirin may decrease the PI3K/AKT/BIM signaling pathways, then promote osimertinib resistant cells apoptosis. The current study aims to evaluate the combination of aspirin and osimertinib in patients with EGFR/T790M mutations.
Name: Osimertinib
Description: Osimertinib, also known as azd9291, is a 3rd-generation EGFR-TKI used to treat NSCLC patients with resistance to 1st generation EGFR-TKI due to T790M mutation. It has been approved in clinical applications by the FDA in 2015.Type: Drugosimertinib and aspirin
Name: Aspirin
Description: Aspirin, also known as acetylsalicylic acid (ASA), is a very safe medication used to treat pain, fever, or inflammation.Type: Drugosimertinib and aspirin
Description: To evaluate the response to therapy and 1 year median progression-free survival(PFS) rates of the combination of Osimertinib and Aspirin in patients who harbors T790M EGFR-mutant with metastatic pulmonary adenocarcinoma disease progression to 1st generation EGFR-TKI .
Measure: 1-year median progression-free survival(PFS) rates according to resist 1.1 Time: 3yearsDescription: To evaluate the response to therapy and 1 year progression-free survival (PFS) of the combination of Osimertinib and Aspirin in patients who harbors T790M EGFR-mutant with metastatic pulmonary adenocarcinoma disease progression to 1st generation EGFR-TKI .
Measure: median PFS according to resist 1.1 Time: 3yearsDescription: To evaluate the response to therapy and overall survival(OS) of the combination of Osimertinib and Aspirin in patients who harbors T790M EGFR-mutant with metastatic pulmonary adenocarcinoma disease progression to 1st generation EGFR-TKI
Measure: median overall survival(OS) according to resist 1.1 Time: 3yearsSingle Group Assignment
There are 2 SNPs
Previous study showed that one principal mechanism accounting for majority of acquired resistance to Osimertinib in lung cancer is mediated by an exon 20 C797S mutation etc(PMID 29596911). --- C797S ---
A Phase II,Single-arm Study to Evaluate the Efficacy of the Combination of Osimertinib and Aspirin in Patients With Disease Progression to 1st Generation EGFR-TKI Due to Acquisition of EGFR T790M. --- T790M ---
Combination of Osimertinib and Aspirin to Treat 1st Generation Epidermal Growth Factor Receptor-tyrosine Kinase Inhibitor(EGFR-TKI)Resistance Non-small Cell Lung Cancer ( NSCLC) The third generation epidermal growth gactor receptor-tyrosine Kinase Inhibitor(EGFR-TKI) osimertinib has obvious curative effect for EGFR sensitive mutation and T790M mutation(PMID 27959700), but acquired drug resistance will occur. --- T790M ---
The current study aims to evaluate the combination of aspirin and osimertinib in patients with EGFR/T790M mutations. --- T790M ---
To evaluate the response to therapy and 1 year median progression-free survival(PFS) rates of the combination of Osimertinib and Aspirin in patients who harbors T790M EGFR-mutant with metastatic pulmonary adenocarcinoma disease progression to 1st generation EGFR-TKI .. median PFS according to resist 1.1. --- T790M ---
To evaluate the response to therapy and 1 year progression-free survival (PFS) of the combination of Osimertinib and Aspirin in patients who harbors T790M EGFR-mutant with metastatic pulmonary adenocarcinoma disease progression to 1st generation EGFR-TKI .. median overall survival(OS) according to resist 1.1. --- T790M ---
To evaluate the response to therapy and overall survival(OS) of the combination of Osimertinib and Aspirin in patients who harbors T790M EGFR-mutant with metastatic pulmonary adenocarcinoma disease progression to 1st generation EGFR-TKI. --- T790M ---
Non-Small Cell Lung Cancer Stage IIIB Non-small Cell Lung Cancer Stage IV EGFR T790M Lung Neoplasms Carcinoma, Non-Small-Cell Lung Reversible small-molecule EGF receptor tyrosine kinase inhibitors (EGFR-TKI) have shown dramatic therapeutic efficacy in non-small cell lung cancer (NSCLC) patients with EGFR-activating mutations, and have been recommended as the standard first-line therapy in these patients. --- T790M ---
Osimertinib is a 3rd-generation EGFR-TKI used to treat NSCLC patients with resistance to 1st generation EGFR-TKI due to T790M mutation. --- T790M ---
Here, investigators'group observed that in clinic, several patients who took osimertinib and aspirin together have shown excellent effect.Investigators therefore conduct this clinical trial to observe whether the combination of Aspirin and Osimertinib could enhance efficacy of Osimertinib in lung cancer patients resistant to 1st generation EGFR-TKI with T790M. --- T790M ---