89P IMmunotherapy response associated clinical and biological PREdictive factors in advanced SARComas: A retrospective multicenter study

As immunotherapy continues to play an increasingly prominent role in the standard care for various cancers, its effectiveness in unselected sarcomas has been disappointing, with objective response rates (ORR) ranging from 10-15%. However, some outlying responders were reported, suggesting a critical challenge in refining patient selection. This involves the identification of reliable response predictors. The IMPRESARC study, a retrospective and multicenter cohort analysis, included all patients treated with immune checkpoint inhibitors (ICI) for advanced sarcomas across six different centers in France from October 2015 to December 2023 (Centre Léon Bérard, Institut Curie, Institut Gustave Roussy, IUCT Oncopôle, Institut de Cancérologie de l’Ouest). Our aim was to identify clinical and biological factors associated with responses to ICI. A total of 272 patients were included, displaying an ORR of 17%, a disease control rate of 49% (according to RECIST 1.1), a median progression-free survival (PFS) of 2.7 months, and a median overall survival of 13.5 months. Remarkably, 32% of patients were still alive at 24 months, and 27% at 36 months, with 15% experiencing a response duration exceeding 12 months. Factors independently associated with PFS included dNLR, WHO performance status, histologic subtype, and associated treatment. Alveolar soft part sarcoma correlated with better PFS, while dedifferentiated liposarcoma (ddLPS) was linked to worse PFS. Concomitant chemotherapy was associated with a decline in PFS. Molecular biology data, available for only about a third of the patients, were not included in the multivariate analysis. In this subset of patients, RB1 alterations were associated with worse PFS in univariate analysis, while tumor mutational burden did not seem prognostic in terms of PFS. This large cohort reports a promising signal of activity for the use of ICI in ASPS, contrasting with poor prognostic factors such as ddLPS histology, concomitant chemotherapy, high WHO performance status and dNLR scores. These response predictors should be considered to refine therapeutic approaches, but further investigations are needed to identify reliable biomarkers.