Circulating tumor DNA in unresectable pancreatic cancer is a strong predictor of first-line treatment efficacy: The KRASCIPANC prospective study

Abstract

BackgroundThere is no robust predictor of response to chemotherapy (CT) in unresectable pancreatic adenocarcinomas (UPA). The objective of the KRASCIPANC study was to analyze the kinetics of cell-free DNA (cfDNA)/circulating tumor DNA (ctDNA) as a predictor of response to CT in UPA. MethodsBlood samples were collected just before first CT and at day 28. The primary endpoint was the kinetics of KRAS-mutated ctDNA by digital droplet PCR between D0 and D28 as a predictor of progression-free survival (PFS). ResultsWe analyzed 65 patients with a KRAS-mutated tumor. A high level of cfDNA and KRAS-mutated ctDNA at D0, as well as the presence of KRAS-mutated ctDNA at D28, were strongly associated with lower centralized disease control rate (cDCR), shorter cPFS and OS in multivariate analysis. A score combining cfDNA level at diagnosis ≥ or <30 ng/mL and presence or not of KRAS-mutated ctDNA at D28 was an optimal predictor of cDCR (OR=30.7, IC95% 4.31–218 P=.001), PFS (HR=6.79, IC95% 2.76–16.7, P<.001) and OS (HR=9.98, IC95% 4.14–24.1, P<.001). ConclusionA combined score using cfDNA level at diagnosis and KRAS-mutated ctDNA at D28 is strongly associated with patient survival/response to chemotherapy in UPA. Trial RegistrationClinicalTrials.gov Identifier: NCT04560270