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Activity of PD1 inhibitor therapy in advanced sarcoma: a single-center retrospective analysis
Dionisia Quiroga1,2, David A Liebner1,2,3, Jennifer S Philippon1
1The Ohio State University Comprehensive Cancer Center, The Ohio State University, 410 W 12th Avenue, Columbus, OH, 43210, USA.
Background:
Sarcomas constitute a heterogeneous group of tumors with different clinical behaviors and variable responses to systemic therapies. Recent immunotherapy studies with PD1 inhibitors (PD1i) show promising results with use in certain soft-tissue sarcomas; however, the clinical and molecular features that best predict response to PD1i remain unclear.
Methods:
Demographic, imaging, histologic, and genetic sequencing data was collected for sarcoma patients who received nivolumab or pembrolizumab (PD1i) treatment at our institution between January 1st 2015 and April 23rd 2018. The primary objective was to determine progression-free survival (PFS) in patients with advanced sarcomas receiving PD1i. Secondary objectives included determining overall survival (OS) and assessment of characteristics associated with response to PD1i. Fifty-six patients who were treated with PD1i therapy met inclusion criteria for this study.
Results:
Partial response towards PD1i treatment was seen in 3 in 26 evaluable patients, but no complete responses were observed (overall response rate 11.5%). Within this group of patients, the 90 day PFS was found to be 48.8%. In patients in whom PD1 expression was known, there was a statistically significant positive correlation between expression of PD1 and longer PFS and OS rates. Patients that were treated with more than four cycles of PD1i therapy were also more likely to have a greater OS.
Conclusions:
This study suggests activity of PD1i in a pretreated cohort of advanced sarcoma patients, particularly for the subset of patients with PD1 positive tumors. Our results highlight the importance of further research to better target the optimal patient population and markers of response.
Insights
This study found that PD1 inhibitors (PD1i) show activity in advanced sarcoma patients. PD1 positive tumors correlated with longer progression-free survival (PFS) and overall survival (OS) in patients receiving PD1 inhibitors.
Area of Science:
- Oncology
- Immunotherapy
- Cancer Genomics
Background:
- Sarcomas are diverse tumors with variable treatment responses.
- Immunotherapy with PD1 inhibitors shows promise in certain sarcomas.
- Predictive biomarkers for PD1 inhibitor response in sarcoma are not well-defined.
Purpose of the Study:
- To evaluate the efficacy of PD1 inhibitors in advanced sarcoma patients.
- To identify clinical and molecular features associated with response to PD1 inhibitors.
- To determine progression-free survival (PFS) and overall survival (OS) in sarcoma patients treated with PD1 inhibitors.
Main Methods:
- Retrospective analysis of sarcoma patients treated with nivolumab or pembrolizumab (PD1 inhibitors).
- Data collected included demographics, imaging, histology, and genetic sequencing.
- Fifty-six patients met inclusion criteria; primary endpoint was PFS.
Main Results:
- Overall response rate to PD1 inhibitors was 11.5% (3 partial responses in 26 evaluable patients).
- 90-day PFS was 48.8%.
- PD1 expression positively correlated with longer PFS and OS; patients receiving >4 cycles had greater OS.
Conclusions:
- PD1 inhibitors demonstrate activity in pretreated advanced sarcoma patients.
- PD1-positive tumors are associated with better outcomes.
- Further research is needed to optimize patient selection and identify response biomarkers.
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