Circulating KRAS G12D but not G12V is associated with survival in metastatic pancreatic ductal adenocarcinoma-Reference-Cited by-同舟云学术

Circulating KRAS G12D but not G12V is associated with survival in metastatic pancreatic ductal adenocarcinoma

Published:2024-07-09 Issue:1 Volume:15 Page:
ISSN:2041-1723
Container-title:Nature Communications
language:en
Short-container-title:Nat Commun

Author:

Till Jacob E.^ORCID,McDaniel Lee,Chang Changgee^ORCID,Long Qi^ORCID,Pfeiffer Shannon M.^ORCID,Lyman Jaclyn P.,Padrón Lacey J.,Maurer Deena M.,Yu Jia Xin,Spencer Christine N.,Gherardini Pier Federico^ORCID,Da Silva Diane M.^ORCID,LaVallee Theresa M.,Abbott Charles,Chen Richard O.^ORCID,Boyle Sean M.^ORCID,Bhagwat Neha,Cannas Samuele^ORCID,Sagreiya Hersh,Li Wenrui,Yee Stephanie S.,Abdalla Aseel,Wang Zhuoyang,Yin Melinda,Ballinger Dominique,Wissel Paul,Eads Jennifer,Karasic Thomas^ORCID,Schneider Charles,O’Dwyer Peter^ORCID,Teitelbaum Ursina,Reiss Kim A.,Rahma Osama E.,Fisher George A.,Ko Andrew H.,Wainberg Zev A.,Wolff Robert A.,O’Reilly Eileen M.^ORCID,O’Hara Mark H.^ORCID,Cabanski Christopher R.^ORCID,Vonderheide Robert H.^ORCID,Carpenter Erica L.^ORCID

Abstract

AbstractWhile high circulating tumor DNA (ctDNA) levels are associated with poor survival for multiple cancers, variant-specific differences in the association of ctDNA levels and survival have not been examined. Here we investigate KRAS ctDNA (ctKRAS) variant-specific associations with overall and progression-free survival (OS/PFS) in first-line metastatic pancreatic ductal adenocarcinoma (mPDAC) for patients receiving chemoimmunotherapy (“PRINCE”, NCT03214250), and an independent cohort receiving standard of care (SOC) chemotherapy. For PRINCE, higher baseline plasma levels are associated with worse OS for ctKRAS G12D (log-rank p = 0.0010) but not G12V (p = 0.7101), even with adjustment for clinical covariates. Early, on-therapy clearance of G12D (p = 0.0002), but not G12V (p = 0.4058), strongly associates with OS for PRINCE. Similar results are obtained for the SOC cohort, and for PFS in both cohorts. These results suggest ctKRAS G12D but not G12V as a promising prognostic biomarker for mPDAC and that G12D clearance could also serve as an early biomarker of response.

Publisher

Springer Science and Business Media LLC

Link

https://www.nature.com/articles/s41467-024-49915-5.pdf

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