Early Noninvasive Tracking of Response to Targeted Therapy in Non-Small Cell Lung Cancer

Abstract There has been a longstanding need to develop improved methods for the rapid detection of response to anti-cancer therapies. Circulating tumor DNA based liquid biopsies allow for longitudinal monitoring of response to treatment. In this report, we analyzed plasma samples of 25 patients with advanced non-small cell lung cancer and observed that molecular responders had changes in circulating tumor DNA on therapy. We evaluated pre-treatment and post-treatment specimens from patients using allele frequency (AF), as well as the number of mutant molecules per mL of plasma (MMPM) to understand relative changes in response to therapy. AF and MMPM clearance correlated with time to treatment failure and best overall radiographic response in our cohort. Furthermore, among patients with EGFR mutations, lack of clearance in EGFR mutant variants in plasma was associated with earlier treatment failure on the oral tyrosine kinase inhibitor osimertinib. These analyses provide a more comprehensive approach for evaluating therapeutic response to targeted therapies and have important implications for the management of cancer patients and disease monitoring.