Immune Checkpoint Inhibition (Ici) In Advanced Cutaneous Squamous Cell Carcinoma (Cscc): Clinical Response And Correlative Biomarker Analysis.
JOURNAL OF CLINICAL ONCOLOGY(2018)
摘要
9564 Background: ICI has shown major benefit in cutaneous malignancies including melanoma and Merkel cell carcinoma. Efficacy data in cSCC is, however, limited. Here we report our institutional experience of anti-PD-1 therapy in patients (pts) with advanced cSCC, and biomarker analysis. Methods: We conducted a retrospective analysis of cSCC pts treated with nivolumab or pembrolizumab at Massachusetts General Hospital. NGS and IHC for PD-L1 expression and immune cell composition were performed, and correlation with response was analyzed. Results: 13 cSCC pts treated with ICI were identified, 7 of whom had predisposing conditions: CLL or other lymphoma (n = 3), xeroderma pigmentosum (n = 2), and Marjolin’s ulcer (n = 2). 8 pts were treated with pembrolizumab and 5 with nivolumab. 9 pts (69%) had prior cytotoxic chemotherapy or cetuximab. At median follow-up of 16.5 months, 7 pts (62%) achieved objective responses with 2 complete responses. 4 pts had stable disease over 6 months and 2 had primary resistance. 12-month progression-free survival (PFS) and overall survival (OS) was 68.4 % and 83.3%, respectively. Median PFS and OS were not reached. Grade ≥ 3 adverse events were observed in 3 pts (23%), including 1 treatment-related death (myocarditis). Pre-treatment tissues were available for 11 pts. CD4, CD8 T cells and Tregs were present in variable frequencies and showed no association with response. PD-L1 expression in either tumor (TC) or immune cells (IC) was observed in most pts (78%). Mean TC and IC PD-L1 expression in responders vs nonresponders was 11.5 vs 0% and 5 vs 5%, respectively. TC but not IC PD-L1 expression correlated with response (cut-off 1%, p = 0.04). TP53, PIK3CA, DKN2A, and TERT promoter alterations were common. Tumor mutation burden analysis is underway, and its correlation to response will be analyzed. Conclusions: Our single institution “real-world” experience with anti-PD-1 therapy in advanced cSCC shows promising activity, including in pts who would not be eligible for clinical trial enrollment. PD-L1 expression was common and TC expression correlated with response. Further molecular analysis to identify potential predictive biomarkers is ongoing.
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关键词
squamous cell carcinoma,correlative biomarker analysis
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