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Histologic and immunologic factors associated with response to immune checkpoint inhibitors in advanced sarcoma.
Histologic and immunologic factors associated with response to immune checkpoint inhibitors in advanced sarcoma. Clinical cancer research : an official journal of the American Association for Cancer Research Lee, A. Q., Hao, C., Pan, M., Ganjoo, K. N., Bui, N. Q. 2024Abstract
To characterize factors associated with response to immune checkpoint inhibitors (ICIs) in advanced sarcoma.This is a retrospective study with a cohort of 216 patients with advanced sarcoma treated with ICIs between 2016-2023 at Stanford Health Care. Overall survival (OS), progression free survival (PFS), objective response rates per RECIST criteria (ORR), and reason for ICI discontinuation were analyzed across histologic subtypes, ICI regimens, tumor mutational burden (TMB), and PD-L1 expression.The overall ORR in the cohort was 16.7%. The histologic subtypes with the highest ORR were Kaposi sarcoma (KS, 66.7%), alveolar soft part sarcoma (ASPS, 50%), angiosarcoma (AS, 33.3%), myxofibrosarcoma (MFS, 28.6%), and undifferentiated pleomorphic sarcoma (UPS, 27.8%). The subtypes with the lowest ORR were osteosarcoma (0%), synovial sarcoma (SS, 0%), and liposarcoma (LPS, 3.7%). The subtypes with the highest median PFS were KS (median not reached, NR), ASPS (NR), MFS (27.4 months), and UPS (11.3 months). The ORR for sarcomas with PD-L1 = 1% was 27.8% (p=0.02), while the ORR for sarcomas with TMB = 10 mutations per megabase of DNA (mut/MB) was 28.6% (p=0.20).ORR and PFS were highly variable across sarcoma histologic subtype. In this large analysis, KS, ASPS, AS, MFS, and UPS demonstrated the highest ORR and longest PFS while osteosarcoma, SS, and LPS had the lowest ORR and shortest PFS. PD-L1 expression was also associated with increased ORR. Our findings provide further insight into understanding the sarcoma histologic and immunologic factors that correspond with response to ICIs.
View details for DOI 10.1158/1078-0432.CCR-24-3485
View details for PubMedID 39699310