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

Camille Evrard; Pierre Ingrand; Tristan Rochelle; Marine Martel; Gaëlle Tachon; Nicolas Flores; Violaine Randrian; Aurélie Ferru; Paul-Arthur Haineaux; Jean-Michel Goujon; Lucie Karayan-Tapon; David Tougeron

doi:10.1016/j.dld.2023.03.011

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

Dig Liver Dis. 2023 Nov;55(11):1562-1572. doi: 10.1016/j.dld.2023.03.011. Epub 2023 Jun 10.

Authors

Affiliations

¹ Medical Oncology Department, Poitiers University Hospital, Poitiers 86000, France; ProDicET, UR 24144, University of Poitiers, Poitiers 86000, France. Electronic address: [email protected].
² Department of Statistics, Faculty of Medicine, University of Poitiers, Poitiers 86000, France.
³ Cancer Biology Department, Poitiers University Hospital, Poitiers 86000, France.
⁴ Cancer Biology Department, Poitiers University Hospital, Poitiers 86000, France; Cancer Biology Department, Centre Léon Bérard, Lyon 69000, France.
⁵ Department of Imaging, University Hospital of Poitiers, Poitiers 86000, France.
⁶ ProDicET, UR 24144, University of Poitiers, Poitiers 86000, France; Hepato-Gastroenterology Department, Poitiers University Hospital, Poitiers, France.
⁷ Medical Oncology Department, Poitiers University Hospital, Poitiers 86000, France.
⁸ Hepato-Gastroenterology Department, Poitiers University Hospital, Poitiers, France; Hepato-Gastroenterology Department, Poitiers University Hospital, Châtellerault Hospital, Poitiers 86106, France.
⁹ Department of Pathology, Poitiers University Hospital, Poitiers 86000, France.
¹⁰ ProDicET, UR 24144, University of Poitiers, Poitiers 86000, France; Cancer Biology Department, Poitiers University Hospital, Poitiers 86000, France.
¹¹ ProDicET, UR 24144, University of Poitiers, Poitiers 86000, France; Hepato-Gastroenterology Department, Poitiers University Hospital, Poitiers, France. Electronic address: [email protected].

PMID: 37308396
DOI: 10.1016/j.dld.2023.03.011

Abstract

Background: There 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.

Methods: Blood 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).

Results: We 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).

Conclusion: A 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 registration: ClinicalTrials.gov Identifier: NCT04560270.

Keywords: Circulating tumor DNA; Digital droplet PCR; KRAS mutation; Pancreatic cancer.

MeSH terms

Adenocarcinoma* / drug therapy
Adenocarcinoma* / genetics
Biomarkers, Tumor / genetics
Cell-Free Nucleic Acids* / therapeutic use
Circulating Tumor DNA* / genetics
Humans
Mutation
Pancreatic Neoplasms* / drug therapy
Pancreatic Neoplasms* / genetics
Pancreatic Neoplasms* / pathology
Prognosis
Prospective Studies
Proto-Oncogene Proteins p21(ras) / genetics

Substances

Circulating Tumor DNA
Proto-Oncogene Proteins p21(ras)
Cell-Free Nucleic Acids
Biomarkers, Tumor

Associated data

ClinicalTrials.gov/NCT04560270