Resistance Mechanisms After Lorlatinib in ALK-Positive NSCLC

This study focuses on patients with ALK-positive non-small cell lung cancer (NSCLC) that is either locally advanced or has spread to other parts of the body. The main goal is to understand the resistance mechanisms against the first-line treatment using a drug called lorlatinib. The study also aims to evaluate the effectiveness and safety of subsequent treatments given after the cancer becomes resistant to lorlatinib. This research is important as it could help improve treatment strategies and patient care for ALK-positive NSCLC in a real-world setting. In this observational study, participants will undergo resistance assessment through liquid biopsies, specifically blood tests to examine circulating tumor DNA using a method called NGS. If applicable, tissue biopsies will also be conducted for further NGS testing. The study aims to identify the progression pattern and molecular mechanisms of resistance to lorlatinib. This includes understanding both primary resistance (when the drug doesn't work from the start) and acquired resistance (when the drug stops working after some time). The study will also compare the mechanisms of primary and acquired resistance.