1654P Analysis of predictive biomarkers for immune checkpoint inhibitor therapy in several subtypes of sarcomas

Abstract

The significance of predictive biomarkers when using immune checkpoint inhibitors (ICI) is becoming increasingly prominent. Clinical trials of ICI have been performed in sarcomas, such as (SARC028). However, most results have been negative for the reason that few have taken biomarkers into account. We analysed and evaluated data for immunotherapy biomarkers in several sarcomas subtypes. 172 samples from patients with sarcomas have been collected in China since February 2018. Tumour mutation burden was detected and measured by next generation sequencing (NGS). MSI status was evaluated by NGS covering 500 MSI loci. Expression of PD-L1 was detected using Dako PD-L1 IHC 22C3 pharmDx. PD-L1 expression was determined using the percentage of viable tumour cells stained, termed as Tumor Proportion Score (TPS). TPS score was defined as: strong positive ≥50%, moderate positive ≥5% and <50%, weak positive ≥1% and <5%, and negative <1%. Among these patients, 59% (101/172) male and 41% (71/172) female had 18 fibrosarcomas, 50 liposarcomas, 25 rhabdomyosarcomas, 18 synovial sarcomas, 28 osteosarcomas, 21 soft tissue sarcomas (STS) and 12 Ewing sarcomas. All these patients had microsatellite-stable tumours, and all had low TMB level (median 3.2 mutants/Mb, average 3.5 Mutants/Mb). PD-L1 expression in fibrosarcoma was 66.7% negative, 16.7% weak positive, 5.6% moderate positive, and 11.1 strong positive. In Liposarcoma it was 85.7% negative, 8.6% weak positive, 2.7% moderate positive, 2.7% strong positive. In Rhabdomyosarcoma it was 96.0% negative, 4% moderate positive. In synovial sarcoma tumours were 100% negative for PD-L1 expression. In Osteosarcoma levels were 78.6% negative, 7.4% weak positive, 10.1% moderate positive, 3.6% strong positive. In STS it was 80.9% negative, and 19.0% weak positive. In Ewing sarcoma it was 91.7% negative, 8.3% weak positive. Biomarkers for ICI therapy, such as TMB level, MSS/MSI status, and PD-L1 expression, were present in a low proportion of sarcomas, suggesting other predictive biomarkers need to be explored and applied to stratify and select patients suitable for ICI therapy in this tumour type.