1. Circulating KRAS G12D but not G12V is associated with survival in metastatic pancreatic ductal adenocarcinoma.
- Author
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Till JE, McDaniel L, Chang C, Long Q, Pfeiffer SM, Lyman JP, Padrón LJ, Maurer DM, Yu JX, Spencer CN, Gherardini PF, Da Silva DM, LaVallee TM, Abbott C, Chen RO, Boyle SM, Bhagwat N, Cannas S, Sagreiya H, Li W, Yee SS, Abdalla A, Wang Z, Yin M, Ballinger D, Wissel P, Eads J, Karasic T, Schneider C, O'Dwyer P, Teitelbaum U, Reiss KA, Rahma OE, Fisher GA, Ko AH, Wainberg ZA, Wolff RA, O'Reilly EM, O'Hara MH, Cabanski CR, Vonderheide RH, and Carpenter EL
- Subjects
- Humans, Female, Male, Middle Aged, Aged, Prognosis, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Mutation, Progression-Free Survival, Neoplasm Metastasis, Carcinoma, Pancreatic Ductal genetics, Carcinoma, Pancreatic Ductal mortality, Carcinoma, Pancreatic Ductal blood, Carcinoma, Pancreatic Ductal pathology, Carcinoma, Pancreatic Ductal drug therapy, Proto-Oncogene Proteins p21(ras) genetics, Pancreatic Neoplasms genetics, Pancreatic Neoplasms blood, Pancreatic Neoplasms mortality, Pancreatic Neoplasms pathology, Pancreatic Neoplasms drug therapy, Circulating Tumor DNA blood, Circulating Tumor DNA genetics, Biomarkers, Tumor blood, Biomarkers, Tumor genetics
- 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., (© 2024. The Author(s).)
- Published
- 2024
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