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

被引：3

作者：

Till, Jacob E. ^{[1
]}

McDaniel, Lee ^{[2
]}

Chang, Changgee ^{[3
]}

Long, Qi ^{[1
]}

Pfeiffer, Shannon M. ^{[4
]}

Lyman, Jaclyn P. ^{[4
]}

Padron, Lacey J. ^{[4
]}

Maurer, Deena M. ^{[4
]}

Yu, Jia Xin ^{[4
]}

Spencer, Christine N. ^{[4
]}

Gherardini, Pier Federico ^{[4
]}

Da Silva, Diane M. ^{[4
]}

LaVallee, Theresa M. ^{[4
]}

Abbott, Charles ^{[2
]}

Chen, Richard O. ^{[2
]}

Boyle, Sean M. ^{[2
]}

Bhagwat, Neha ^{[1
]}

Cannas, Samuele ^{[1
]}

Sagreiya, Hersh ^{[1
]}

Li, Wenrui ^{[1
]}

Yee, Stephanie S. ^{[1
]}

Abdalla, Aseel ^{[1
]}

Wang, Zhuoyang ^{[1
]}

Yin, Melinda ^{[1
]}

Ballinger, Dominique ^{[1
]}

Wissel, Paul ^{[1
]}

Eads, Jennifer ^{[1
]}

Karasic, Thomas ^{[1
]}

Schneider, Charles ^{[1
]}

O'Dwyer, Peter ^{[1
]}

Teitelbaum, Ursina ^{[1
]}

Reiss, Kim A. ^{[1
]}

Rahma, Osama E. ^{[5
]}

Fisher, George A. ^{[6
]}

Ko, Andrew H. ^{[7
]}

Wainberg, Zev A. ^{[8
]}

Wolff, Robert A. ^{[9
]}

O'Reilly, Eileen M. ^{[10
]}

O'Hara, Mark H. ^{[1
]}

Cabanski, Christopher R. ^{[4
]}

Vonderheide, Robert H. ^{[1
]}

Carpenter, Erica L. ^{[1
]}

机构：

[1] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA

[2] Personalis Inc, Menlo Pk, CA USA

[3] Indiana Univ Sch Med, Indianapolis, IN USA

[4] Parker Inst Canc Immunotherapy, San Francisco, CA USA

[5] Dana Farber Canc Inst, Boston, MA USA

[6] Stanford Univ, Stanford, CA USA

[7] Univ Calif San Francisco, San Francisco, CA USA

[8] Univ Calif Los Angeles, Los Angeles, CA USA

[9] Univ Texas MD Anderson Canc Ctr, Houston, TX USA

[10] Mem Sloan Kettering Canc Ctr, New York, NY USA

来源：

NATURE COMMUNICATIONS | 2024年 / 15卷 / 01期

关键词：

TUMOR; DNA; IMMUNOTHERAPY; DYNAMICS; BENEFIT; BURDEN;

D O I：

10.1038/s41467-024-49915-5

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：12

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