Nature Communications (Jul 2024)
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. Da 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,
- Erica L. Carpenter
Affiliations
- Jacob E. Till
- Abramson Cancer Center of the University of Pennsylvania
- Lee McDaniel
- Personalis, 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. Da Silva
- Parker Institute for Cancer Immunotherapy
- Theresa M. LaVallee
- Parker Institute for Cancer Immunotherapy
- Charles Abbott
- Personalis, Inc.
- Richard O. Chen
- Personalis, Inc.
- Sean M. Boyle
- Personalis, 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
- University of California, San Francisco
- Zev A. Wainberg
- University of California, 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
- DOI
- https://doi.org/10.1038/s41467-024-49915-5
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 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.
