Abstract
Immune checkpoint inhibitors, especially the programmed cell death receptor-1/ligand 1 (PD-1/L1) inhibitors, displayed promising efficacy in several solid tumor types and hematological malignancies. Data related to their activity in soft-tissue sarcomas (STS) are scarce.We performed a pooled analysis of clinical trials investigating a PD1 or PD-L1 antagonist in patients with advanced STS. Three hundred eighty-four patients were included in the pooled analysis; of those, 153 (39.8%) received a PD1/PD-L1 antagonist as a single agent. In patients treated with anti-PD1/PDL1 as a single agent, the overall response rate (ORR) and non-progression rate (NPR) were 15.1% and 58.5% respectively. In patients treated with a combination regimen, the ORR and NPR were 13.4% and 55.8% respectively. Analysis by histological subtype revealed that patients with alveolar soft part sarcoma and undifferentiated pleomorphic sarcoma exhibited the highest response rates and leiomyosarcoma the lowest. PD-L1 expression rate was low and inconsistently associated with objective response.PD-1/PD-L1 antagonists have limited activity in unselected STS. Future studies should implement histology and immune-based stratification of STS in their design as well as sequential blood and tissue sampling to better understand the mechanisms of resistance and response given sarcomas inherent heterogeneity.
Highlights
Immune checkpoint inhibitors, especially the programmed cell death receptor-1/ligand 1 (PD-1/L1) inhibitors, displayed promising efficacy in several solid tumor types and hematological malignancies
We report a pooled analysis of these studies in order to get insight on the global activity of Programmed cell death 1 (PD1)/progressive disease (PD)-L1 in soft-tissue sarcomas (STS) and according to histological subtype
These results do not suggest an association between the overall response rate (ORR) and the investigational strategy
Summary
Especially the programmed cell death receptor-1/ligand 1 (PD-1/L1) inhibitors, displayed promising efficacy in several solid tumor types and hematological malignancies. PD-L1 targeting in soft-tissue sarcoma (STS) patients have been recently reported. We report a pooled analysis of these studies in order to get insight on the global activity of PD1/PD-L1 in STS and according to histological subtype.
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