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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Elsevier
2024-12-01
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| Series: | The Journal of Liquid Biopsy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2950195424000262 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Andrea De Giglio |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-2c56aaec253547179fef60b4afe1ddfb |
| institution | OA Journals |
| issn | 2950-1954 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
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| series | The Journal of Liquid Biopsy |
| spelling | doaj-art-2c56aaec253547179fef60b4afe1ddfb2025-08-20T01:58:34ZengElsevierThe Journal of Liquid Biopsy2950-19542024-12-01610016110.1016/j.jlb.2024.100161Early monitoring of plasma KRAS G12C with digital PCR predicts antitumor response to immunotherapy or sotorasib in advanced NSCLC: A brief reportAndrea De Giglio0Federico Zacchini1Giulia Venturi2Alessandro Di Federico3Claudia Parisi4Filippo Gustavo Dall’Olio5Ilaria Ricciotti6Valentina Favorito7Ambrogio Gagliano8Dario De Biase9Thais Maloberti10Annalisa Altimari11Elisa Gruppioni12Giovanni Tallini13Barbara Melotti14Francesca Sperandi15Francesco Gelsomino16Lorenzo Montanaro17Andrea Ardizzoni18Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Corresponding author. Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.Departmental Program in Laboratory Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, ItalyDepartment of Medical and Surgical Sciences, University of Bologna, Bologna, ItalyDepartment of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, ItalyDepartment of Medical Oncology, Gustave Roussy, Villejuif, France; Faculty of Medicine, Paris-Saclay University, Paris, FranceDepartment of Medical Oncology, Gustave Roussy, Villejuif, FranceDepartment of Medical and Surgical Sciences, University of Bologna, Bologna, ItalyDepartment of Medical and Surgical Sciences, University of Bologna, Bologna, ItalyDepartment of Medical and Surgical Sciences, University of Bologna, Bologna, ItalySolid Tumor Molecular Pathology Laboratory, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Department of Pharmacy and Biotechnology, University of Bologna, Bologna, ItalySolid Tumor Molecular Pathology Laboratory, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, ItalySolid Tumor Molecular Pathology Laboratory, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, ItalySolid Tumor Molecular Pathology Laboratory, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, ItalyDepartment of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; Solid Tumor Molecular Pathology Laboratory, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, ItalyMedical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, ItalyMedical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, ItalyMedical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, ItalyDepartment of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; Departmental Program in Laboratory Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, ItalyDepartment of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, ItalyBackground: 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.http://www.sciencedirect.com/science/article/pii/S2950195424000262Non-small cell lung cancerLiquid biopsyImmunotherapyKras |
| spellingShingle | 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 Early monitoring of plasma KRAS G12C with digital PCR predicts antitumor response to immunotherapy or sotorasib in advanced NSCLC: A brief report The Journal of Liquid Biopsy Non-small cell lung cancer Liquid biopsy Immunotherapy Kras |
| title | Early monitoring of plasma KRAS G12C with digital PCR predicts antitumor response to immunotherapy or sotorasib in advanced NSCLC: A brief report |
| title_full | Early monitoring of plasma KRAS G12C with digital PCR predicts antitumor response to immunotherapy or sotorasib in advanced NSCLC: A brief report |
| title_fullStr | Early monitoring of plasma KRAS G12C with digital PCR predicts antitumor response to immunotherapy or sotorasib in advanced NSCLC: A brief report |
| title_full_unstemmed | Early monitoring of plasma KRAS G12C with digital PCR predicts antitumor response to immunotherapy or sotorasib in advanced NSCLC: A brief report |
| title_short | Early monitoring of plasma KRAS G12C with digital PCR predicts antitumor response to immunotherapy or sotorasib in advanced NSCLC: A brief report |
| title_sort | early monitoring of plasma kras g12c with digital pcr predicts antitumor response to immunotherapy or sotorasib in advanced nsclc a brief report |
| topic | Non-small cell lung cancer Liquid biopsy Immunotherapy Kras |
| url | http://www.sciencedirect.com/science/article/pii/S2950195424000262 |
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