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Clin Cancer Res. 2020 Jan 3. pii: clincanres.1824.2019. doi: 10.1158/1078-0432.CCR-19-1824. [Epub ahead of print]

Correlative Analyses of the SARC028 Trial Reveal an Association Between Sarcoma-Associated Immune Infiltrate and Response to Pembrolizumab.

Author information

1
Surgical Oncology, The University of Texas MD Anderson Cancer Center.
2
Medicine, Division of Hematology/Oncology, U Pittsburgh.
3
The University of Texas MD Anderson Cancer Center.
4
n/a, Cancer Research And Biostatistics.
5
Internal Medicine, Washington University in St. Louis.
6
Hematology/Oncology, University of Michigan-Ann Arbor.
7
Hematology/Oncology, Mayo Clinic.
8
Department of Internal Medicine/Division of Medical Oncology, Duke University Health System.
9
University of Southern California Norris Comprehensive Cancer Center.
10
Mayo Clinic.
11
Medical Oncology, MedStar Washington Hospital Center.
12
Memorial Sloan Kettering Cancer Center.
13
Knight Cancer Institute, Oregon Health & Science University.
14
Sarcoma, Moffitt Cancer Center.
15
Thoracic/Head & Neck Medical Oncology, University of Texas MD Anderson Cancer Center.
16
Surgical Oncology, University of Texas MD Anderson Cancer Center.
17
President, SARC.
18
Pathology, The University of Texas MD Anderson Cancer Center.
19
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center.
20
Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center HTawbi@mdanderson.org.

Abstract

PURPOSE:

We recently reported a 17.5 % objective RECIST 1.1 response rate in a Phase II study of pembrolizumab in patients with advanced sarcoma (SARC028). The majority of responses occurred in undifferentiated pleomorphic sarcoma (UPS) and dedifferentiated liposarcoma (DDLPS). We sought to determine whether we can identify immune features that correlate with clinical outcomes from tumor tissues obtained pre- and on-treatment.

EXPERIMENTAL DESIGN:

Pretreatment (n=78) and 8-week on-treatment (n=68) tumor biopsies were stained for PD-L1 and multiplex immunofluorescence panels. The density of positive cells was quantified to determine associations with anti-PD-1 response.

RESULTS:

Patients that responded to pembrolizumab were more likely to have higher densities of activated T cells (CD8+ CD3+ PD-1+) and increased percentage of tumor associated macrophages (TAMs) expressing PD-L1 pre-treatment compared to non-responders. Pre-treatment tumors from responders also exhibited higher densities of effector memory cytotoxic T cells and regulatory T cells compared to non-responders. Additionally, higher density of cytotoxic tumor infiltrating T-cells at baseline correlated with a better progression-free survival (PFS).

CONCLUSIONS:

We show that quantitative assessments of CD8+ CD3+ PD-1+ T cells, % TAMs expressing PD-L1, and other T cell densities correlate with sarcoma response to pembrolizumab and improved PFS. Our findings support that multiple cell types present at the start of treatment may enhance tumor regression following anti-PD-1 therapy in specific advanced sarcomas. Efforts to confirm the activity of pembrolizumab in an expansion cohort of UPS/DDLPS patients are underway.

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