Early monitoring of plasma KRAS G12C with digital PCR predicts antitumor response to immunotherapy or sotorasib in advanced NSCLC: A brief report

Early monitoring of plasma KRAS G12C with digital PCR predicts antitumor response to immunotherapy or sotorasib in advanced NSCLC: A brief report

Background: The frontline management of non-oncogene addicted non-small cell lung cancer (NSCLC) involves immune-checkpoint inhibitors (ICI) alone or combined with chemotherapy (CT-ICI). The dynamic landscape of KRAS-positive NSCLC presents a spectrum of treatment options, including ICIs, targeted t...

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Main Authors: Andrea De Giglio, Federico Zacchini, Giulia Venturi, Alessandro Di Federico, Claudia Parisi, Filippo Gustavo Dall’Olio, Ilaria Ricciotti, Valentina Favorito, Ambrogio Gagliano, Dario De Biase, Thais Maloberti, Annalisa Altimari, Elisa Gruppioni, Giovanni Tallini, Barbara Melotti, Francesca Sperandi, Francesco Gelsomino, Lorenzo Montanaro, Andrea Ardizzoni
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:The Journal of Liquid Biopsy
Subjects:
Non-small cell lung cancer
Liquid biopsy
Immunotherapy
Kras
Online Access:http://www.sciencedirect.com/science/article/pii/S2950195424000262
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Summary:Background: The frontline management of non-oncogene addicted non-small cell lung cancer (NSCLC) involves immune-checkpoint inhibitors (ICI) alone or combined with chemotherapy (CT-ICI). The dynamic landscape of KRAS-positive NSCLC presents a spectrum of treatment options, including ICIs, targeted therapy and combination strategies currently under investigation. Methods: We conducted a prospective project to detect circulating tumor DNA (ctDNA) in patients with KRAS G12C, advanced NSCLC. We included patients undergoing upfront ICIs or subsequent line sotorasib. We planned three-time points: baseline (T0), after 3 months of treatment (T1) and at disease progression (T2). Results: 24 consecutive patients have been included. The most frequent baseline characteristics were: nonsquamous histology (95.8%), male gender (62.5%), ECOG PS 0–1 (79.2%), <3 metastatic sites (13/24, 54.2%). 18 patients (75%) received ICI-based strategies and 6 patients (25%) sotorasib. Patients with liver metastases (p ​= ​0.01) and those with >3 metastatic sites (p ​= ​0.002) exhibited significantly elevated ctDNA. Median overall survival (OS) was 7.5 months, progression-free survival (PFS) was 4.0 months and the objective response rate (ORR) was 33.3%. Higher AF correlated with an increased risk of death (HR 1.04, p ​= ​0.03), though not progression. The mOS was 7.5 months (95% CI, 1.91-NR) in high-AF group and 11.3 months (95% CI, 6.6-NR) in low-AF group (p ​= ​0.38). Notably, a reduction in plasma DNA levels was significantly associated with objective response (p ​= ​0.01). Two patients received a T2 dosage showing increased ctDNA levels after a previous reduction associated with response. Conclusion: Early monitoring with ctDNA may offer potential benefits in the evolving scenario of KRAS G12C NSCLC treatment.
ISSN:2950-1954

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