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dc.rights.licenseopenen_US
hal.structure.identifierInstitut Bergonié [Bordeaux]
hal.structure.identifierUniversité de Bordeaux [UB]
dc.contributor.authorITALIANO, Antoine
hal.structure.identifierExplicyte Immuno-Oncology [Bordeaux]
dc.contributor.authorGUEGAN, Jean-Philippe
hal.structure.identifierInstitut Universitaire du Cancer de Toulouse - Oncopole [IUCT Oncopole - UMR 1037]
dc.contributor.authorVALENTIN, Thibaud
hal.structure.identifierDépartement d’Innovation Thérapeutique et essais précoces [Gustave Roussy] [DITEP]
dc.contributor.authorBAHLEDA, Rastilav
hal.structure.identifierHôpital Morvan - CHRU de Brest [CHU - BREST ]
dc.contributor.authorMETGES, Jean Philippe
hal.structure.identifierCentre Léon Bérard [Lyon]
dc.contributor.authorCASSIER, Philippe Alexandre
hal.structure.identifierInstitut Bergonié [Bordeaux]
dc.contributor.authorTOULMONDE, Maud
hal.structure.identifierInstitut Bergonié [Bordeaux]
dc.contributor.authorSPALATO-CERUSO, Mariella
hal.structure.identifierInstitut Bergonié [Bordeaux]
hal.structure.identifierUniversité de Bordeaux [UB]
dc.contributor.authorPEYRAUD, Florent
hal.structure.identifierInstitut Bergonié [Bordeaux]
dc.contributor.authorPALUSSIÈRE, Jean
hal.structure.identifierInstitut Bergonié [Bordeaux]
dc.contributor.authorKIND, Michèle
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorCANTAREL, Coralie
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorBELLERA, Carine
hal.structure.identifierImmuSmol
dc.contributor.authorBESSEDE, Alban
dc.date.accessioned2024-09-17T12:38:36Z
dc.date.available2024-09-17T12:38:36Z
dc.date.created2024-06-01
dc.date.conference2024-05-31
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/201626
dc.description.abstractEn11516 Background: Vascular Endothelial Growth Factor (VEGF)-driven angiogenesis is a pivotal factor in creating an immunosuppressive tumor microenvironment. Approximately 80% of Soft Tissue Sarcomas (STS) are characterized by a 'cold' microenvironment, lacking tertiary lymphoid structures (TLS). While the efficacy of VEGF pathway and PD-1/PD-L1 axis blockade has been established in various tumor types, their impact on 'cold' STS remains unexplored. This study aims to evaluate the synergistic effect of anti-angiogenesis and PD-1 blockade in altering the microenvironment of cold STS, potentially enhancing immune response and therapeutic efficacy. Methods: In this phase II, single-arm, open-label, multicentric trial, we explored the efficacy and safety of combining regorafenib (R) and avelumab (A) in advanced TLS-negative STS patients. Patients were administered 160 mg of R daily for 3 weeks in a 4-week cycle, alongside 10 mg/kg of A biweekly. Endpoints included high-throughput analysis of tumor and plasma samples, response rate, progression-free survival (PFS), overall survival (OS), and safety, as per the NCI-CTCAE v5.0 guidelines. Results: From May 2019 to August 2021, 49 TLS-negative STS patients were enrolled, including leiomyosarcoma (45%), synovial sarcoma (18%), and other subtypes. The median age was 57.1 years, with patients having undergone an average of 2 prior treatment lines. High-throughput analysis of sequential plasma samples indicated an upregulation of immune-inducing protein biomarkers such as CXCL10 and soluble CD8 antigen. Multiplex immunofluorescence analysis of sequential tumor samples revealed significant increase in CD8 T cell infiltration on-treatment. The most common severe adverse events were grade 1 or 2 palmar-plantar erythrodysesthesia, fatigue, and diarrhea. The median follow-up was 7.1 months, with 32.6% of patients experiencing tumor shrinkage, and a clinical benefit rate of 48.8%. The 6-month PFS was 22.1%, with a median OS of 15.1 months. Conclusions: The combination of regorafenib and avelumab demonstrates a marked mobilization of antitumor immunity in patients with TLS-negative STS. The observed efficacy appears superior to that of single-agent immune checkpoint inhibition in 'cold' STS, and higher than the 6-month PFS benchmark of 14% set by EORTC. This indicates the potential effectiveness of this treatment combination in managing advanced cold STS, marking a significant stride in precision immunotherapy for this group of tumors. Clinical trial information: NCT03475953 .
dc.language.isoENen_US
dc.title.enReshaping the tumor microenvironment of cold soft-tissue sarcomas with anti-VEGFR targeted therapy: A Phase 2 Trial of Regorafenib combined with avelumab.
dc.typePosteren_US
dc.identifier.doi10.1200/JCO.2024.42.16_suppl.11516en_US
dc.subject.halSciences du Vivant [q-bio]/Canceren_US
dc.subject.halSciences du Vivant [q-bio]/Immunologie/Immunothérapieen_US
dc.subject.halSciences du Vivant [q-bio]/Médecine humaine et pathologieen_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.conference.titleAmerican society of clinical oncology Annual meeting 2024en_US
bordeaux.countryusen_US
bordeaux.teamEPICENE_BPHen_US
bordeaux.conference.cityChicagoen_US
bordeaux.import.sourcehal
hal.identifierhal-04694549
hal.version1
hal.invitednonen_US
hal.conference.organizerAmerican Society of Clinical Oncology (ASCO)en_US
hal.conference.end2024-06-04
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exportfalse
workflow.import.sourcehal
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.au=ITALIANO,%20Antoine&GUEGAN,%20Jean-Philippe&VALENTIN,%20Thibaud&BAHLEDA,%20Rastilav&METGES,%20Jean%20Philippe&rft.genre=unknown


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