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Published on: September 25, 2018
PD1/PD-L1 targeting in advanced soft-tissue sarcomas: a pooled analysis of phase II trials
Antoine Italiano1,2, Carine Bellera3,4, Sandra D'Angelo5,6
1Early Phase Trials and Sarcoma Units, Institut Bergonié, 229 Cours de l'Argonne, Bordeaux, France. a.italiano@bordeaux.unicancer.fr.
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.
Insights
Programmed cell death receptor-1/ligand 1 (PD-1/L1) inhibitors show limited efficacy in advanced soft-tissue sarcomas (STS). Future research should focus on histology and immune markers for better patient stratification and treatment strategies.
Area of Science:
- Oncology
- Immunotherapy
- Sarcoma Research
Background:
- Immune checkpoint inhibitors, particularly PD-1/L1 antagonists, have shown success in various cancers.
- Data on their efficacy in soft-tissue sarcomas (STS) are limited.
- This study pooled clinical trial data to evaluate PD-1/L1 inhibitors in advanced STS patients.
Discussion:
- Pooled analysis included 384 patients with advanced STS.
- Single-agent PD-1/L1 therapy yielded an overall response rate (ORR) of 15.1% and non-progression rate (NPR) of 58.5%.
- Combination regimens showed similar efficacy (ORR 13.4%, NPR 55.8%).
Key Insights:
- Specific STS subtypes like alveolar soft part sarcoma and undifferentiated pleomorphic sarcoma responded better than leiomyosarcoma.
- PD-L1 expression was low and inconsistently correlated with response.
- Overall, PD-1/L1 antagonists demonstrated limited activity in unselected STS populations.
Outlook:
- Future STS trials require histology-based and immune-based patient stratification.
- Sequential sampling of blood and tissue is crucial to understand resistance and response mechanisms.
- Addressing sarcoma heterogeneity is key for optimizing immunotherapy strategies.
