Study of Primary Resistance Mechanisms to Third-generation EGFR-TKIs as First Treatment in Advanced EGFR-positive Non-small Cell Lung Cancer

What this Trial Is About

Lung cancer is the leading cause of cancer-related deaths worldwide, with non-small cell lung cancer NSCLC making up 80%-85% of cases. This research aims to understand why about 20% of patients with EGFR-positive NSCLC do not respond to third-generation EGFR tyrosine kinase inhibitors EGFR-TKIs as their first treatment. The study seeks to identify molecular markers that predict who will benefit from these drugs and to clarify the mechanisms behind this primary resistance to guide treatment decisions. Patients with advanced EGFR-positive NSCLC will receive third-generation EGFR-TKIs such as Osimertinib, Almonertinib, or Furmonertinib as their initial therapy. Tumor tissue collected at diagnosis will be analyzed using next-generation gene sequencing to detect genomic profiles. Blood plasma samples taken before treatment and after one month of therapy will also be examined for circulating tumor DNA to assess response and resistance. Participants will be monitored over several years, with key measurements including objective response rate and progression-free survival assessed up to 3 years, and overall survival tracked for 5 years. Researchers will compare genetic differences in tumor and blood samples between patients who respond and those resistant to treatment. Patients will provide clinical, imaging, and sample data, and will be followed to evaluate treatment impact and disease progression.

Exploring the Mechanism of Primary Resistance to Third-generation EGFR-TKIs as First-line Treatment in EGFR-positive Advanced NSCLC (PRECISE Study)