Early changes in circulating tumor DNA predict response of KRAS G12C mutated NSCLC to adagrasib

Non-invasive monitoring of circulating tumor DNA has the potential to be a readily available measure for early prediction of clinical response to treatment. Analysis of early ctDNA changes in patients receiving adagrasib for KRAS G12C-mutated non-small cell lung cancer in cohort A of the KRYSTAL-1 clinical trial found that a maximal response could be observed during the initial approximately 3-week treatment period, well before the first scan at 6 weeks. Patients with complete ctDNA clearance at cycle 2 had improved ORR compared with patients with incomplete ctDNA clearance (60.6% versus 33.3%). Complete ctDNA clearance at cycle 4 was associated with improved overall survival (14.7 versus 5.4 months). The authors conclude that early plasma response of ctDNA can predict clinical outcomes.