Lung cancer is currently the world's largest malignant tumor for cancer-related deaths with non-small cell lung cancer (NSCLC) accounting for 80%-85%. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), especially the 3rd-generation EGFR-TKIs have demonstrated strong antitumor effects in EGFR-positive patients.
However, approximately 20% of EGFR-positive were primarily resistant to 3rd generation EGFR-TKIs, i.e., clinical non-response or disease progression in the short term.
This study aimed to clarify the molecular indicators that predict the benefits of 3-rd EGFR-TKIs as first-line therapy in NSCLCpatients with EGFR-positive. Further, to clarify their primary drug resistance mechanisms, which is of great significance for the treatment and clinical decision-making of NSCLC disease.
Age >18 years;
Histological or cytopathological diagnosed NSCLC;
According to the American Joint Committee on Cancer (AJCC) eighth edition of the Lung Cancer Staging Manual, the clinical stage is unresectable IIIB-IV or recurrence and metastasis after surgery;
At least one measurable lesion can be evaluated according to the Response Evaluation Criteria In Solid Tumours v1.1 (RECIST1.1) criteria;
Patients who cannot understand the content of the experiment and cannot cooperate, and those who refuse to sign the informed consent form;
Pregnant and lactating women;
Other malignant neoplastic diseases within 3 years;
Patients who have undergone other clinical drug trials;
Stage IIIB-IV EGFR-positive lung patients receiving 3rd generation EGFR-TKIs (Osimertinib 80mg/Qd or Almonertinib 110mg/Qd or Furmonertinib 80mg/Qd) as first-line therapy.
Cohort
Prospective
Genomic profiles detection
Other interventionThe Paraffin-embedded tumor tissue at diagnosis is collected and assessed by Next- generation gene sequencing
circulating tumor DNA detection
Other interventionThe Plasma at diagnosis and at 1-month treatment are collected and assessed by Next-generation gene sequencing
Objective Response Rate (ORR)
The proportion of patients with a complete response or partial response to treatment according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
Progression-free survival (PFS)
Time from the beginning of treatment to the first disease progression (PD) in patients with advanced NSCLC
Differences in genomic profiles of tumor tissues and ctDNA clearance of third-generation EGFR-TKIs sensitive and primary drug-resistant NSCLC.
The patients who don't achieve partial response or progress within 6 months are defined as the primary resistant group. The genomic profiles and ctDNA clearance detected by Next-generation gene sequencing will be compared between the primary drug-resistant group and sensitive-drug group.
Overall survival (OS)
Overall survival (OS) is defined as the duration from the beginning of first-line immunotherapy until death due to any cause. Subjects who are still alive at the end of the study observation period will be censored at the time of last known vital status
Disease Control Rate (DCR)
The proportion of patients with a complete response or partial response or stable desease to treatment according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
The correlation between tumor microenvironment signature and efficacy of 3rd EGFR-TKIs
The baseline paraffin-embedded tissue is collected and assessed by multiplex immunohistochemistry, including T lymphocytes, B lymphocytes, NK lymphocytes, macrophagocyte, and DC cells. And explore the association between tumor microenvironment signature and primary resistance and the efficacy of 3rd EGFR-TKIs during the enrolled observation process.
Click on the lead sponsor to view all of their trials.
Second Xiangya Hospital of Central South University
Lead sponsor
Xiangya Hospital of Central South University
Collaborator
Shanghai Chest Hospital
Collaborator
West China Hospital
Collaborator
Hunan Cancer Hospital
Collaborator
The Third Xiangya Hospital of Central South University
Collaborator
The First Affiliated Hospital of Xiamen University
Collaborator
Second Affiliated Hospital, School of Medicine, Zhejiang University
Collaborator
China-Japan Friendship Hospital
Collaborator
Fudan University
Collaborator
First Affiliated Hospital of Kunming Medical University
Collaborator
Loudi Central Hospital
Collaborator
ZhuZhou Central Hospital
Collaborator
Xiangtan Central Hospital
Collaborator
First People's Hospital of Chenzhou
Collaborator
Yueyang Central Hospital
Collaborator
Yongzhou Central Hospital
Collaborator
The First Affiliated Hospital of University of South China
Collaborator
Hunan Provincial People's Hospital
Collaborator
Shaoyang Central Hospital
Collaborator
Yiyang Central Hospital
Collaborator
Changsha Central Hospital
Collaborator
The First People's Hospital of Guiyang
Collaborator
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Collaborator
Renmin Hospital of Wuhan University
Collaborator
The First People's Hospital of Changde City
Collaborator
Zhuzhou Second Hospital
Collaborator
First Hospital of Changsha
Collaborator
Hengyang Central Hospital
Collaborator
Huaihua first people's Hospital
Collaborator
The First People's Hospital of Xiangtan
Collaborator
University of South China Affiliated Nanhua Hospital
Collaborator
Xiangxi Autonomous Prefecture People's Hospital
Collaborator
People's Hospital of Zhangjiajie
Collaborator
Second People's Hospital Of Huaihua
Collaborator
Hunan Academy of Traditional Chinese Medicine Affiliated Hospital
Collaborator
The Third Hospital of Changsha
Collaborator
Xiangya Changde Hospital
Collaborator
Changsha County first People's Hospital
Collaborator
Hunan Provincial Straight Hospital of Traditional Chinese Medicine
Collaborator
Liuyang Hospital of traditional Chinese Medicine
Collaborator
Second People's Hospital of Hunan
Collaborator
First Affiliated Hospital of Guangxi Medical University
Collaborator
Guiyang Public Health Treatment Center
Collaborator
The Affiliated Bethune Hospital of Shanxi Medical University
Collaborator
Hunan University of Traditional Chinese Medicine
Collaborator
Tongji Hospital
Collaborator
The First Affiliated Hospital of Nanchang University
Collaborator
