Liquid Biopsy-Driven Cetuximab Rechallenge Strategy in Molecularly Selected Metastatic Colorectal Cancer Patients
BackgroundRechallenge with EGFR inhibitors represents a promising strategy for patients with RAS wild type (WT) colorectal cancer (CRC) but definitive selection criteria are lacking. Recently, the RAS WT status on circulating tumor DNA (ct-DNA) emerged as a potential watershed for this strategy. Our...
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.852583/full |
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| author | Stefano Mariani Marco Puzzoni Riccardo Giampieri Pina Ziranu Valeria Pusceddu Clelia Donisi Mara Persano Giovanna Pinna Erika Cimbro Alissa Parrino Dario Spanu Andrea Pretta Eleonora Lai Nicole Liscia Alessio Lupi Enrica Giglio Grazia Palomba Milena Casula Marina Pisano Giuseppe Palmieri Mario Scartozzi |
| author_facet | Stefano Mariani Marco Puzzoni Riccardo Giampieri Pina Ziranu Valeria Pusceddu Clelia Donisi Mara Persano Giovanna Pinna Erika Cimbro Alissa Parrino Dario Spanu Andrea Pretta Eleonora Lai Nicole Liscia Alessio Lupi Enrica Giglio Grazia Palomba Milena Casula Marina Pisano Giuseppe Palmieri Mario Scartozzi |
| author_sort | Stefano Mariani |
| collection | DOAJ |
| description | BackgroundRechallenge with EGFR inhibitors represents a promising strategy for patients with RAS wild type (WT) colorectal cancer (CRC) but definitive selection criteria are lacking. Recently, the RAS WT status on circulating tumor DNA (ct-DNA) emerged as a potential watershed for this strategy. Our study explored the liquid biopsy-driven cetuximab rechallenge in a RAS and BRAF WT selected population.MethodsCRC patients with RAS and BRAF WT both on tumor tissue and on ct-DNA at baseline receiving rechallenge with cetuximab were eligible for our analysis. Ct-DNA was analyzed for RAS-BRAF mutations with pyro-sequencing and nucleotide sequencing assays. Real-time PCR and droplet digital PCR were performed to confirm the RAS-BRAF mutational status.ResultsA total of 26 patients were included in our analysis. In the global population, RR was 25.0%, median overall survival (mOS) was 5.0 months, and median progression-free survival (mPFS) was 3.5 months. Previous response to anti-EGFR was associated with improved mPFS (5.0 vs. 2.0 months, HR: 0.26, p = 0.048); anti-EGFR free interval > 14 months and anti-EGFR free interval > 16 months were associated with improved mPFS (respectively 7.0 vs. 3.0 months, HR: 0.27, p = 0.013 and not reached vs. 3.0 months, HR: 0.20, p = 0.002) and with improved mOS (respectively 13.0 vs. 5.0 months, HR: 0.27, p = 0.013 and 13.0 vs. 5.0 months, HR: 0.20, p = 0.002). Previous lines >2 were correlated with improved mPFS (4.0 vs. 1.0 month, HR: 0.05, p = 0.041) and with improved mOS (7.0 vs. 1.0 month, HR: 0.045, p = 0.034). In a multiple logistic regression model, only the anti-EGFR free interval was confirmed to be a significant predictor for mOS and mPFS.ConclusionsLiquid biopsy-driven cetuximab rechallenge was confirmed to be effective. The clinical outcome was consistent with available results from phase II studies. In addition to the molecular selection through the analysis of ct-DNA for RAS, the long anti-EGFR free interval is confirmed as a prospective selection criterion for this therapeutic option. |
| first_indexed | 2024-12-10T03:44:19Z |
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| id | doaj.art-7c74f9145f1d405983f83568cd2f0eab |
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| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-10T03:44:19Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj.art-7c74f9145f1d405983f83568cd2f0eab2022-12-22T02:03:27ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-04-011210.3389/fonc.2022.852583852583Liquid Biopsy-Driven Cetuximab Rechallenge Strategy in Molecularly Selected Metastatic Colorectal Cancer PatientsStefano Mariani0Marco Puzzoni1Riccardo Giampieri2Pina Ziranu3Valeria Pusceddu4Clelia Donisi5Mara Persano6Giovanna Pinna7Erika Cimbro8Alissa Parrino9Dario Spanu10Andrea Pretta11Eleonora Lai12Nicole Liscia13Alessio Lupi14Enrica Giglio15Grazia Palomba16Milena Casula17Marina Pisano18Giuseppe Palmieri19Mario Scartozzi20Azienda Ospedaliera Universitaria (AOU) Cagliari, University Hospital and University of Cagliari, Cagliari, ItalyAzienda Ospedaliera Universitaria (AOU) Cagliari, University Hospital and University of Cagliari, Cagliari, ItalyMedical Oncology Unit, University Hospital and Università Politecnica delle Marche, Ancona, ItalyAzienda Ospedaliera Universitaria (AOU) Cagliari, University Hospital and University of Cagliari, Cagliari, ItalyAzienda Ospedaliera Universitaria (AOU) Cagliari, University Hospital and University of Cagliari, Cagliari, ItalyAzienda Ospedaliera Universitaria (AOU) Cagliari, University Hospital and University of Cagliari, Cagliari, ItalyAzienda Ospedaliera Universitaria (AOU) Cagliari, University Hospital and University of Cagliari, Cagliari, ItalyAzienda Ospedaliera Universitaria (AOU) Cagliari, University Hospital and University of Cagliari, Cagliari, ItalyAzienda Ospedaliera Universitaria (AOU) Cagliari, University Hospital and University of Cagliari, Cagliari, ItalyAzienda Ospedaliera Universitaria (AOU) Cagliari, University Hospital and University of Cagliari, Cagliari, ItalyAzienda Ospedaliera Universitaria (AOU) Cagliari, University Hospital and University of Cagliari, Cagliari, ItalyAzienda Ospedaliera Universitaria (AOU) Cagliari, University Hospital and University of Cagliari, Cagliari, ItalyAzienda Ospedaliera Universitaria (AOU) Cagliari, University Hospital and University of Cagliari, Cagliari, ItalyAzienda Ospedaliera Universitaria (AOU) Cagliari, University Hospital and University of Cagliari, Cagliari, ItalyMedical Oncology Unit, University Hospital and Università Politecnica delle Marche, Ancona, ItalyMedical Oncology Unit, University Hospital and Università Politecnica delle Marche, Ancona, ItalyUnit of Cancer Genetics and Institute of Biomolecular Chemistry (ICB), National Research Council (CNR), Sassari, ItalyUnit of Cancer Genetics and Institute of Biomolecular Chemistry (ICB), National Research Council (CNR), Sassari, ItalyUnit of Cancer Genetics and Institute of Biomolecular Chemistry (ICB), National Research Council (CNR), Sassari, ItalyUnit of Cancer Genetics and Institute of Biomolecular Chemistry (ICB), National Research Council (CNR), Sassari, ItalyAzienda Ospedaliera Universitaria (AOU) Cagliari, University Hospital and University of Cagliari, Cagliari, ItalyBackgroundRechallenge with EGFR inhibitors represents a promising strategy for patients with RAS wild type (WT) colorectal cancer (CRC) but definitive selection criteria are lacking. Recently, the RAS WT status on circulating tumor DNA (ct-DNA) emerged as a potential watershed for this strategy. Our study explored the liquid biopsy-driven cetuximab rechallenge in a RAS and BRAF WT selected population.MethodsCRC patients with RAS and BRAF WT both on tumor tissue and on ct-DNA at baseline receiving rechallenge with cetuximab were eligible for our analysis. Ct-DNA was analyzed for RAS-BRAF mutations with pyro-sequencing and nucleotide sequencing assays. Real-time PCR and droplet digital PCR were performed to confirm the RAS-BRAF mutational status.ResultsA total of 26 patients were included in our analysis. In the global population, RR was 25.0%, median overall survival (mOS) was 5.0 months, and median progression-free survival (mPFS) was 3.5 months. Previous response to anti-EGFR was associated with improved mPFS (5.0 vs. 2.0 months, HR: 0.26, p = 0.048); anti-EGFR free interval > 14 months and anti-EGFR free interval > 16 months were associated with improved mPFS (respectively 7.0 vs. 3.0 months, HR: 0.27, p = 0.013 and not reached vs. 3.0 months, HR: 0.20, p = 0.002) and with improved mOS (respectively 13.0 vs. 5.0 months, HR: 0.27, p = 0.013 and 13.0 vs. 5.0 months, HR: 0.20, p = 0.002). Previous lines >2 were correlated with improved mPFS (4.0 vs. 1.0 month, HR: 0.05, p = 0.041) and with improved mOS (7.0 vs. 1.0 month, HR: 0.045, p = 0.034). In a multiple logistic regression model, only the anti-EGFR free interval was confirmed to be a significant predictor for mOS and mPFS.ConclusionsLiquid biopsy-driven cetuximab rechallenge was confirmed to be effective. The clinical outcome was consistent with available results from phase II studies. In addition to the molecular selection through the analysis of ct-DNA for RAS, the long anti-EGFR free interval is confirmed as a prospective selection criterion for this therapeutic option.https://www.frontiersin.org/articles/10.3389/fonc.2022.852583/fullcolorectal (colon) cancerepidermal growth factor receptor (EGFR)RASliquid biopsyrechallengecetuximab |
| spellingShingle | Stefano Mariani Marco Puzzoni Riccardo Giampieri Pina Ziranu Valeria Pusceddu Clelia Donisi Mara Persano Giovanna Pinna Erika Cimbro Alissa Parrino Dario Spanu Andrea Pretta Eleonora Lai Nicole Liscia Alessio Lupi Enrica Giglio Grazia Palomba Milena Casula Marina Pisano Giuseppe Palmieri Mario Scartozzi Liquid Biopsy-Driven Cetuximab Rechallenge Strategy in Molecularly Selected Metastatic Colorectal Cancer Patients Frontiers in Oncology colorectal (colon) cancer epidermal growth factor receptor (EGFR) RAS liquid biopsy rechallenge cetuximab |
| title | Liquid Biopsy-Driven Cetuximab Rechallenge Strategy in Molecularly Selected Metastatic Colorectal Cancer Patients |
| title_full | Liquid Biopsy-Driven Cetuximab Rechallenge Strategy in Molecularly Selected Metastatic Colorectal Cancer Patients |
| title_fullStr | Liquid Biopsy-Driven Cetuximab Rechallenge Strategy in Molecularly Selected Metastatic Colorectal Cancer Patients |
| title_full_unstemmed | Liquid Biopsy-Driven Cetuximab Rechallenge Strategy in Molecularly Selected Metastatic Colorectal Cancer Patients |
| title_short | Liquid Biopsy-Driven Cetuximab Rechallenge Strategy in Molecularly Selected Metastatic Colorectal Cancer Patients |
| title_sort | liquid biopsy driven cetuximab rechallenge strategy in molecularly selected metastatic colorectal cancer patients |
| topic | colorectal (colon) cancer epidermal growth factor receptor (EGFR) RAS liquid biopsy rechallenge cetuximab |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.852583/full |
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