Relationship between T790M Mutation in Advanced Lung Adenocarcinoma and Clinical Characteristics after EGFR-TKI Resistance and its Effect on mPFS and mOS

Abstract

Background: Lung adenocarcinoma (LUAD) is a form of non-small cell lung cancer. Patients develop drug resistance during long-term treatment, which is associated with T790M mutations. This study aimed to assess the correlation between T790M mutation in advanced LUAD and clinical features after epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance, and its effect on median progressive free survival (mPFS) and median overall survival (mOS). Methods: A total of 164 patients diagnosed with advanced LUAD who developed resistance to EGFR-TKI therapy were recruited in this study. These patients received EGFR-TKI therapy at the Zhejiang Rongjun Hospital, China from May 2020 to March 2022. Based on the presence or absence of the T790M mutation, they were divided into two groups: the T790M (–) (n = 70) and T790M (+) (n = 94). A droplet digital polymerase chain reaction (ddPCR) was performed, and subsequently, the EGFR mutation was evaluated using the ∆Ct value (Ct mutation-CT external control). The correlation between T790M mutation and clinical characteristics following EGFR-TKI resistance was determined. Moreover, the impact of T790M mutation on prognosis, as well as on median progressive free survival (mPFS) and median overall survival (mOS), was also observed. Results: The carcinoembryonic antigen (CEA) levels, history of smoking, Eastern Cooperative Oncology Group (ECOG) score and the pattern of disease progression after developing drug resistance were identified as the main risk factors for positive T790M mutation. Under 50% probability of survival, the patients with negative T790M mutations had mPFS of 14.0 months and mOS of 21.0 months, whereas patients with positive T790M mutations exhibited mPFS of 38.0 months and mOS of 41.0 months. There were statistically significant mPFS and mOS in patients with T790M-positive mutations compared to the patients with T790M-negative mutations (p < 0.001). Conclusion: The progression of the disease, smoking history, ECOG score and the level of CEA were independent risk factors for T790M mutation in patients with advanced LUAD. Furthermore, these factors also exhibited an impact on both mPFS and mOS of the patients.