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

Autor: Till JE; Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA., McDaniel L; Personalis, Inc., Menlo Park, CA, USA., Chang C; Indiana University School of Medicine, Indianapolis, IN, USA., Long Q; Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA., Pfeiffer SM; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA., Lyman JP; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA., Padrón LJ; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA., Maurer DM; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA., Yu JX; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA., Spencer CN; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA., Gherardini PF; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA., Da Silva DM; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA., LaVallee TM; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA., Abbott C; Personalis, Inc., Menlo Park, CA, USA., Chen RO; Personalis, Inc., Menlo Park, CA, USA., Boyle SM; Personalis, Inc., Menlo Park, CA, USA., Bhagwat N; Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA., Cannas S; Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA., Sagreiya H; Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA., Li W; Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA., Yee SS; Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA., Abdalla A; Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA., Wang Z; Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA., Yin M; Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA., Ballinger D; Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA., Wissel P; Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA., Eads J; Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA., Karasic T; Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA., Schneider C; Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA., O'Dwyer P; Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA., Teitelbaum U; Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA., Reiss KA; Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA., Rahma OE; Dana-Farber Cancer Institute, Boston, MA, USA., Fisher GA; Stanford University, Stanford, CA, USA., Ko AH; University of California, San Francisco, San Francisco, CA, USA., Wainberg ZA; University of California, Los Angeles, Los Angeles, CA, USA., Wolff RA; The University of Texas MD Anderson Cancer Center, Houston, TX, USA., O'Reilly EM; Memorial Sloan Kettering Cancer Center, New York, NY, USA., O'Hara MH; Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA., Cabanski CR; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA., Vonderheide RH; Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA., Carpenter EL; Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA. erical@upenn.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Jul 09; Vol. 15 (1), pp. 5763. Date of Electronic Publication: 2024 Jul 09.
DOI: 10.1038/s41467-024-49915-5
Abstrakt: 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).)
Databáze: MEDLINE
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