Single-center study of circulating tumor DNA-guided de-escalation of targeted therapy in advanced non-small cell lung cancer

Uniterrupted targeted therapy until disease progression or intolerable toxic effects is currently the routine therapy for advanced non-small cell lung cancer (aNSCLC) with driver gene variations. However, development of drug resistance is inevitable. A prospective study at Southern Medical University (Guangzhou, China) evaluated adaptive de-escalation of tyrosine kinase inhibitor (TKI) therapy guided by circulating tumor (ct)DNA in patients with radiologically undetectable aNSCLC after targeted and local consolidative therapy. The trial of 60 patients found a median progression-free survival of 18.4 months, with 23% of patients requiring no additional TKI treatment; 52% receiving intermittent TKI retreatment guided by ctDNA or carcinoembryonic antigen before disease progression, and 25% receiving TKI retreatment due to disease progression. The authors conclude that a ctDNA-guided adaptive de-escalation TKI treatment strategy is feasible for patients with aNSCLC and undetectable ctDNA after targeted and local consolidative therapy.