Activity of PD1 inhibitor therapy in advanced sarcoma: a single-center retrospective analysis

Abstract 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.