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

Publication ,  Journal Article
Keung, EZ; Burgess, M; Salazar, R; Parra, ER; Rodrigues-Canales, J; Bolejack, V; Van Tine, BA; Schuetze, SM; Attia, S; Riedel, RF; Hu, J ...
Published in: Clin Cancer Res
March 15, 2020

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. PATIENTS AND METHODS: 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 (TAM) expressing PD-L1 pre-treatment compared with non-responders. Pre-treatment tumors from responders also exhibited higher densities of effector memory cytotoxic T cells and regulatory T cells compared with non-responders. In addition, 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, percentage of 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 patients with UPS/DDLPS are underway.

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Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

March 15, 2020

Volume

26

Issue

6

Start / End Page

1258 / 1266

Location

United States

Related Subject Headings

  • Young Adult
  • Treatment Outcome
  • Survival Rate
  • Soft Tissue Neoplasms
  • Sarcoma
  • Programmed Cell Death 1 Receptor
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Lymphocytes, Tumor-Infiltrating
 

Citation

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Keung, E. Z., Burgess, M., Salazar, R., Parra, E. R., Rodrigues-Canales, J., Bolejack, V., … Tawbi, H. A. (2020). Correlative Analyses of the SARC028 Trial Reveal an Association Between Sarcoma-Associated Immune Infiltrate and Response to Pembrolizumab. Clin Cancer Res, 26(6), 1258–1266. https://doi.org/10.1158/1078-0432.CCR-19-1824
Keung, Emily Z., Melissa Burgess, Ruth Salazar, Edwin R. Parra, Jaime Rodrigues-Canales, Vanessa Bolejack, Brian A. Van Tine, et al. “Correlative Analyses of the SARC028 Trial Reveal an Association Between Sarcoma-Associated Immune Infiltrate and Response to Pembrolizumab.Clin Cancer Res 26, no. 6 (March 15, 2020): 1258–66. https://doi.org/10.1158/1078-0432.CCR-19-1824.
Keung EZ, Burgess M, Salazar R, Parra ER, Rodrigues-Canales J, Bolejack V, et al. Correlative Analyses of the SARC028 Trial Reveal an Association Between Sarcoma-Associated Immune Infiltrate and Response to Pembrolizumab. Clin Cancer Res. 2020 Mar 15;26(6):1258–66.
Keung, Emily Z., et al. “Correlative Analyses of the SARC028 Trial Reveal an Association Between Sarcoma-Associated Immune Infiltrate and Response to Pembrolizumab.Clin Cancer Res, vol. 26, no. 6, Mar. 2020, pp. 1258–66. Pubmed, doi:10.1158/1078-0432.CCR-19-1824.
Keung EZ, Burgess M, Salazar R, Parra ER, Rodrigues-Canales J, Bolejack V, Van Tine BA, Schuetze SM, Attia S, Riedel RF, Hu J, Okuno SH, Priebat DA, Movva S, Davis LE, Reed DR, Reuben A, Roland CL, Reinke D, Lazar AJ, Wang W-L, Wargo JA, Tawbi HA. Correlative Analyses of the SARC028 Trial Reveal an Association Between Sarcoma-Associated Immune Infiltrate and Response to Pembrolizumab. Clin Cancer Res. 2020 Mar 15;26(6):1258–1266.

Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

March 15, 2020

Volume

26

Issue

6

Start / End Page

1258 / 1266

Location

United States

Related Subject Headings

  • Young Adult
  • Treatment Outcome
  • Survival Rate
  • Soft Tissue Neoplasms
  • Sarcoma
  • Programmed Cell Death 1 Receptor
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Lymphocytes, Tumor-Infiltrating