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

Jacob E. Till, Lee McDaniel, Changgee Chang, Qi Long, Shannon M. Pfeiffer, Jaclyn P. Lyman, Lacey J. Padrón, Deena M. Maurer, Jia Xin Yu, Christine N. Spencer, Pier Federico Gherardini, Diane M. Silva, Theresa M. LaVallee, Charles Abbott, Richard O. Chen, Sean M. Boyle, Neha Bhagwat, Samuele Cannas, Hersh Sagreiya, Wenrui Li, Stephanie S. Yee, Aseel Abdalla, Zhuoyang Wang, Melinda Yin, Dominique Ballinger, Paul Wissel, Jennifer Eads, Thomas Karasic, Charles Schneider, Peter O’Dwyer, Ursina Teitelbaum, Kim A. Reiss, Osama E. Rahma, George A. Fisher, Andrew H. Ko, Zev A. Wainberg, Robert A. Wolff, Eileen M. O’Reilly, Mark H. O’Hara, Christopher R. Cabanski, Robert H. Vonderheide and Erica L. Carpenter ()
Additional contact information
Jacob E. Till: Abramson Cancer Center of the University of Pennsylvania
Lee McDaniel: Inc.
Changgee Chang: Indiana University School of Medicine
Qi Long: Abramson Cancer Center of the University of Pennsylvania
Shannon M. Pfeiffer: Parker Institute for Cancer Immunotherapy
Jaclyn P. Lyman: Parker Institute for Cancer Immunotherapy
Lacey J. Padrón: Parker Institute for Cancer Immunotherapy
Deena M. Maurer: Parker Institute for Cancer Immunotherapy
Jia Xin Yu: Parker Institute for Cancer Immunotherapy
Christine N. Spencer: Parker Institute for Cancer Immunotherapy
Pier Federico Gherardini: Parker Institute for Cancer Immunotherapy
Diane M. Silva: Parker Institute for Cancer Immunotherapy
Theresa M. LaVallee: Parker Institute for Cancer Immunotherapy
Charles Abbott: Inc.
Richard O. Chen: Inc.
Sean M. Boyle: Inc.
Neha Bhagwat: Abramson Cancer Center of the University of Pennsylvania
Samuele Cannas: Abramson Cancer Center of the University of Pennsylvania
Hersh Sagreiya: Abramson Cancer Center of the University of Pennsylvania
Wenrui Li: Abramson Cancer Center of the University of Pennsylvania
Stephanie S. Yee: Abramson Cancer Center of the University of Pennsylvania
Aseel Abdalla: Abramson Cancer Center of the University of Pennsylvania
Zhuoyang Wang: Abramson Cancer Center of the University of Pennsylvania
Melinda Yin: Abramson Cancer Center of the University of Pennsylvania
Dominique Ballinger: Abramson Cancer Center of the University of Pennsylvania
Paul Wissel: Abramson Cancer Center of the University of Pennsylvania
Jennifer Eads: Abramson Cancer Center of the University of Pennsylvania
Thomas Karasic: Abramson Cancer Center of the University of Pennsylvania
Charles Schneider: Abramson Cancer Center of the University of Pennsylvania
Peter O’Dwyer: Abramson Cancer Center of the University of Pennsylvania
Ursina Teitelbaum: Abramson Cancer Center of the University of Pennsylvania
Kim A. Reiss: Abramson Cancer Center of the University of Pennsylvania
Osama E. Rahma: Dana-Farber Cancer Institute
George A. Fisher: Stanford University
Andrew H. Ko: San Francisco
Zev A. Wainberg: Los Angeles
Robert A. Wolff: The University of Texas MD Anderson Cancer Center
Eileen M. O’Reilly: Memorial Sloan Kettering Cancer Center
Mark H. O’Hara: Abramson Cancer Center of the University of Pennsylvania
Christopher R. Cabanski: Parker Institute for Cancer Immunotherapy
Robert H. Vonderheide: Abramson Cancer Center of the University of Pennsylvania
Erica L. Carpenter: Abramson Cancer Center of the University of Pennsylvania

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: Abstract While 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-49915-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49915-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-49915-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().