Early Changes in Circulating Cell-Free KRAS G12C Predict Response to Adagrasib in KRAS Mutant Non-Small Cell Lung Cancer Patients.

Autor:	Paweletz CP; Belfer Center of Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts., Heavey GA; Belfer Center of Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts., Kuang Y; Belfer Center of Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts., Durlacher E; Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts., Kheoh T; Mirati Therapeutics, San Diego, California., Chao RC; Mirati Therapeutics, San Diego, California., Spira AI; Virginia Cancer Specialists Research Institute, Fairfax, Virginia., Leventakos K; Department of Oncology, Mayo Clinic, Rochester, Minnesota., Johnson ML; Sarah Cannon Research Institute Tennessee Oncology, Nashville, Tennessee., Ou SI; Chao Family Comprehensive Cancer Center, University of California-Irvine, Orange, California., Riely GJ; Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, New York., Anderes K; Mirati Therapeutics, San Diego, California., Yang W; Mirati Therapeutics, San Diego, California., Christensen JG; Mirati Therapeutics, San Diego, California., Jänne PA; Belfer Center of Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts.; Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2023 Aug 15; Vol. 29 (16), pp. 3074-3080.
DOI:	10.1158/1078-0432.CCR-23-0795
Abstrakt:	Purpose: Non-invasive monitoring of circulating tumor DNA (ctDNA) has the potential to be a readily available measure for early prediction of clinical response. Here, we report on early ctDNA changes of KRAS G12C in a Phase 2 trial of adagrasib in patients with advanced, KRAS G12C-mutant lung cancer. Experimental Design: We performed serial droplet digital PCR (ddPCR) and plasma NGS on 60 KRAS G12C-mutant patients with lung cancer that participated in cohort A of the KRYSTAL-1 clinical trial. We analyzed the change in ctDNA at 2 specific intervals: Between cycles 1 and 2 and at cycle 4. Changes in ctDNA were compared with clinical and radiographic response. Results: We found that, in general, a maximal response in KRAS G12C ctDNA levels could be observed during the initial approximately 3-week treatment period, well before the first scan at approximately 6 weeks. 35 patients (89.7%) exhibited a decrease in KRAS G12C cfDNA >90% and 33 patients (84.6%) achieved complete clearance by cycle 2. Patients with complete ctDNA clearance at cycle 2 showed an improved objective response rate (ORR) compared with patients with incomplete ctDNA clearance (60.6% vs. 33.3%). Furthermore, complete ctDNA clearance at cycle 4 was associated with an improved overall survival (14.7 vs. 5.4 months) and progression-free survival (HR, 0.3). Conclusions: These results support using early plasma response of KRAS G12C assessed at approximately 3 weeks to anticipate the likelihood of a favorable objective clinical response. (©2023 American Association for Cancer Research.)
Databáze:	MEDLINE
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