Circulating KRAS G12D but not G12V is associated with survival in metastatic pancreatic ductal adenocarcinoma Journal Article
| Authors: | Till, J. E.; McDaniel, L.; Chang, C.; Long, Q.; Pfeiffer, S. M.; Lyman, J. P.; Padrón, L. J.; Maurer, D. M.; Yu, J. X.; Spencer, C. N.; Gherardini, P. F.; Da Silva, D. M.; LaVallee, T. M.; Abbott, C.; Chen, R. O.; Boyle, S. M.; Bhagwat, N.; Cannas, S.; Sagreiya, H.; Li, W.; Yee, S. S.; Abdalla, A.; Wang, Z.; Yin, M.; Ballinger, D.; Wissel, P.; Eads, J.; Karasic, T.; Schneider, C.; O’Dwyer, P.; Teitelbaum, U.; Reiss, K. A.; Rahma, O. E.; Fisher, G. A.; Ko, A. H.; Wainberg, Z. A.; Wolff, R. A.; O’Reilly, E. M.; O’Hara, M. H.; Cabanski, C. R.; Vonderheide, R. H.; Carpenter, E. L. |
| Article Title: | Circulating KRAS G12D but not G12V is associated with survival in metastatic pancreatic ductal adenocarcinoma |
| 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. © The Author(s) 2024. |
| Keywords: | adult; cancer survival; controlled study; human tissue; aged; middle aged; gene mutation; major clinical study; overall survival; genetics; mutation; mortality; systemic therapy; pancreatic neoplasms; antineoplastic agent; allele; tumor localization; metastasis; progression free survival; antineoplastic combined chemotherapy protocols; carcinoma, pancreatic ductal; cohort analysis; genetic variability; pathology; retrospective study; tumor marker; alanine aminotransferase blood level; aspartate aminotransferase blood level; health care quality; alanine aminotransferase; aspartate aminotransferase; blood; dna; biomarker; pancreas tumor; neoplasm metastasis; tumor; drug therapy; k ras protein; personal experience; protein p21; proto-oncogene proteins p21(ras); disease exacerbation; clinical laboratory; plasma; ethnicity; kras protein, human; progression-free survival; pancreas metastasis; pancreatic ductal carcinoma; limit of detection; chemoimmunotherapy; cancer prognosis; response evaluation criteria in solid tumors; nivolumab; humans; prognosis; human; male; female; article; circulating tumor dna; droplet digital polymerase chain reaction; biomarkers, tumor; cell free nucleic acid; sotigalimab; circulating free dna |
| Journal Title: | Nature Communications |
| Volume: | 15 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2024-07-09 |
| Start Page: | 5763 |
| Language: | English |
| DOI: | 10.1038/s41467-024-49915-5 |
| PUBMED: | 38982051 |
| PROVIDER: | scopus |
| PMCID: | PMC11233636 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
