Reshaping the tumor microenvironment of cold soft-tissue sarcomas with anti-VEGFR targeted therapy: A Phase 2 Trial of Regorafenib combined with avelumab
| dc.rights.license | open | en_US |
| dc.contributor.author | ITALIANO, Antoine | |
| dc.contributor.author | GUEGAN, Jean-Philippe | |
| dc.contributor.author | VALENTIN, Thibaud | |
| dc.contributor.author | BAHLEDA, Rastilav | |
| dc.contributor.author | METGES, Jean Philippe | |
| dc.contributor.author | CASSIER, Philippe Alexandre | |
| dc.contributor.author | TOULMONDE, Maud | |
| dc.contributor.author | SPALATO-CERUSO, Mariella | |
| dc.contributor.author | PEYRAUD, Florent | |
| dc.contributor.author | PALUSSIÈRE, Jean | |
| dc.contributor.author | KIND, Michèle | |
| hal.structure.identifier | Bordeaux population health [BPH] | |
| dc.contributor.author | CANTAREL, Coralie | |
| hal.structure.identifier | Bordeaux population health [BPH] | |
| dc.contributor.author | BELLERA, Carine | |
| dc.contributor.author | BESSEDE, Alban | |
| dc.date.accessioned | 2024-10-16T11:40:34Z | |
| dc.date.available | 2024-10-16T11:40:34Z | |
| dc.date.issued | 2024 | |
| dc.date.conference | 2024-05-31 | |
| dc.identifier.issn | 0732-183X | en_US |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/202536 | |
| dc.description.abstractEn | 11516Background: 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.iso | EN | en_US |
| dc.publisher | Asco | en_US |
| dc.title.en | Reshaping the tumor microenvironment of cold soft-tissue sarcomas with anti-VEGFR targeted therapy: A Phase 2 Trial of Regorafenib combined with avelumab | |
| dc.type | Communication dans un congrès | en_US |
| dc.identifier.doi | 10.1200/JCO.2024.42.16_suppl.11516 | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio]/Santé publique et épidémiologie | en_US |
| bordeaux.page | 11516-11516 | en_US |
| bordeaux.volume | 42 | en_US |
| bordeaux.hal.laboratories | Bordeaux Population Health Research Center (BPH) - UMR 1219 | en_US |
| bordeaux.issue | 16_suppl | en_US |
| bordeaux.institution | Université de Bordeaux | en_US |
| bordeaux.institution | INSERM | en_US |
| bordeaux.conference.title | The 2024 ASCO Annual Meeting | en_US |
| bordeaux.country | us | en_US |
| bordeaux.title.proceeding | 2024 ASCO Annual Meeting | en_US |
| bordeaux.team | EPICENE_BPH | en_US |
| bordeaux.conference.city | Chicago | en_US |
| hal.proceedings | oui | en_US |
| hal.conference.organizer | American Society of Clinical Oncology (ASCO) | en_US |
| hal.conference.end | 2024-06-04 | |
| hal.popular | non | en_US |
| hal.audience | Internationale | en_US |
| hal.export | false | |
| dc.rights.cc | Pas de Licence CC | en_US |
| bordeaux.COinS | ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.date=2024&rft.volume=42&rft.issue=16_suppl&rft.spage=11516-11516&rft.epage=11516-11516&rft.eissn=0732-183X&rft.issn=0732-183X&rft.au=ITALIANO,%20Antoine&GUEGAN,%20Jean-Philippe&VALENTIN,%20Thibaud&BAHLEDA,%20Rastilav&METGES,%20Jean%20Philippe&rft.genre=unknown |
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