دورية أكاديمية
Circulating tumor DNA dynamics reveal KRAS G12C mutation heterogeneity and response to treatment with the KRAS G12C inhibitor divarasib in solid tumors.
| العنوان: | Circulating tumor DNA dynamics reveal KRAS G12C mutation heterogeneity and response to treatment with the KRAS G12C inhibitor divarasib in solid tumors. |
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| المؤلفون: | Choi Y; Genentech Inc., South San Francisco, CA, United States., Dharia NV; Genentech, Inc., South San Francisco, CA, United States., Jun T; Genentech Inc., South San Francisco, CA, United States., Chang J; Genentech Inc., South San Francisco, CA, United States., Royer-Joo S; Genentech, Inc., South San Francisco, CA, United States., Yau KK; Roche (Canada), Mississauga, Ontario, Canada., Assaf ZJ; Roche/Genentech, United States., Aimi J; Genentech Inc., South San Francisco, CA, United States., Sivakumar S; Foundation Medicine, Cambridge, MA, United States., Montesion M; Foundation Medicine, Inc., Cambridge, MA, United States., Sacher A; Princess Margaret Cancer Centre, Toronto, ON, Canada., LoRusso P; Yale University, New Haven, CT, United States., Desai J; Peter MacCallum Cancer Centre and the University of Melbourne, Melbourne, Australia., Schutzman JL; Genentech, Inc., South San Francisco, CA, United States., Shi Z; Genentech, Inc., South San Francisco, United States. |
| المصدر: | Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2024 Jul 12. Date of Electronic Publication: 2024 Jul 12. |
| Publication Model: | Ahead of Print |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: The Association Country of Publication: United States NLM ID: 9502500 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1557-3265 (Electronic) Linking ISSN: 10780432 NLM ISO Abbreviation: Clin Cancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Denville, NJ : The Association, c1995- |
| مستخلص: | Purpose: To inform prognosis, treatment response, disease biology, and KRAS G12C mutation heterogeneity, we conducted exploratory circulating tumor DNA (ctDNA) profiling on 134 patients with solid tumors harboring a KRAS G12C mutation treated with single-agent divarasib (GDC-6036) in a phase 1 study. Experimental Design: Plasma samples were collected for serial ctDNA profiling at baseline (Cycle 1 Day 1 prior to treatment) and multiple on-treatment time points (Cycle 1 Day 15 and Cycle 3 Day 1). Results: KRAS G12C ctDNA was detectable from plasma samples in 72.9% (43/59) and 92.6% (50/54) of patients with non-small cell lung cancer and colorectal cancer, respectively, the majority of whom were eligible for study participation based on a local test detecting the KRAS G12C mutation in tumor tissue. Baseline ctDNA tumor fraction was associated with tumor type, disease burden, and metastatic sites. A decline in ctDNA level was observed as early as Cycle 1 Day 15. Serial assessment showed a decline in ctDNA tumor fraction associated with response and progression-free survival. Except for a few cases of KRAS G12C sub-clonality, on-treatment changes in KRAS G12C variant allele frequency mirrored changes in the overall ctDNA tumor fraction. Conclusion: Across tumor types, the KRAS G12C mutation likely represents a truncal mutation in the majority of patients. Rapid and deep decline in ctDNA tumor fraction was observed in patients responding to divarasib treatment. Early on-treatment dynamics of ctDNA were associated with patient outcomes and tumor response to divarasib treatment. |
| تواريخ الأحداث: | Date Created: 20240712 Latest Revision: 20240712 |
| رمز التحديث: | 20240712 |
| DOI: | 10.1158/1078-0432.CCR-24-0255 |
| PMID: | 38995268 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1557-3265 |
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| DOI: | 10.1158/1078-0432.CCR-24-0255 |