Ziv-aflibercept plus pembrolizumab in patients with advanced melanoma resistant to anti-PD-1 treatment.

Autor: Baginska J; Department of Medical Oncology, Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Nau A; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA., Gomez Diaz I; Department of Medical Oncology, Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Giobbie-Hurder A; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA., Weirather J; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA., Vergara J; Department of Medical Oncology, Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Abrecht C; Department of Medical Oncology, Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Hallisey M; Department of Medical Oncology, Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Dennis J; Department of Medical Oncology, Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Severgnini M; Department of Medical Oncology, Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Huezo J; Department of Medical Oncology, Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Marciello I; Department of Medical Oncology, Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Rahma O; Department of Medical Oncology, Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Manos M; Department of Medical Oncology, Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Brohl AS; Sarcoma Department and Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA., Bedard PL; Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada., Renouf DJ; Cancer and Department of Medicine, University of British Columbia, Vancouver, BC, Canada., Sharon E; Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD, USA., Streicher H; Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD, USA., Ott PA; Department of Medical Oncology, Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Buchbinder EI; Department of Medical Oncology, Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Hodi FS; Department of Medical Oncology, Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. stephen_hodi@dfci.harvard.edu.
Jazyk: angličtina
Zdroj: Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2024 Jan 18; Vol. 73 (1), pp. 17. Date of Electronic Publication: 2024 Jan 18.
DOI: 10.1007/s00262-023-03593-2
Abstrakt: Background: Vascular endothelial growth factor is associated with reduced immune response and impaired anti-tumor activity. Combining antiangiogenic agents with immune checkpoint inhibition can overcome this immune suppression and enhance treatment efficacy.
Methods: This study investigated the combination of ziv-aflibercept anti-angiogenic therapy with pembrolizumab in patients with advanced melanoma resistant to anti-PD-1 treatment. Baseline and on-treatment plasma and PBMC samples were analyzed by multiplex protein assay and mass cytometry, respectively.
Results: In this Phase 1B study (NCT02298959), ten patients with advanced PD-1-resistant melanoma were treated with a combination of ziv-aflibercept (at 2-4 mg/kg) plus pembrolizumab (at 2 mg/kg), administered intravenously every 2 weeks. Two patients (20%) achieved a partial response, and two patients (20%) experienced stable disease (SD) as the best response. The two responders had mucosal melanoma, while both patients with SD had ocular melanoma. The combination therapy demonstrated clinical activity and acceptable safety, despite the occurrence of adverse events. Changes in plasma analytes such as platelet-derived growth factor and PD-L1 were explored, indicating potential alterations in myeloid cell function. Higher levels of circulating CXCL10 in non-responding patients may reflect pro-tumor activity. Specific subsets of γδ T cells were associated with poor clinical outcomes, suggesting impaired γδ T-cell function in non-responding patients.
Conclusions: Although limited by sample size and follow-up, these findings highlight the potential of the combination of ziv-aflibercept antiangiogenic therapy with pembrolizumab in patients with advanced melanoma resistant to anti-PD-1 treatment and the need for further research to improve outcomes in anti-PD-1-resistant melanoma.
Trial Registration Number: NCT02298959.
(© 2024. The Author(s).)
Databáze: MEDLINE
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