Abstract 923P
Background
Immune checkpoint inhibition (ICI) with anti-PD-L1 directed therapy has shown promise in SCCHN but only the minority of patients respond to treatment (TX). Understanding the immune responses to these drugs is of critical importance. Prior studies have highlighted the potential anticancer effects of metformin through metabolic alteration in the tumor microenvironment (TME) of SCCHN. This trial was designed to explore the potential multi-mechanistic benefit of the combination of durvalumab (Durva) and metformin (Met) and examine alterations of key immune elements, CD8+ and FoxP3+ T cells, in the TME.
Methods
This is a randomized, single-center trial with planned enrollment of 38 patients with all stages of resectable SCCHN. Patients are randomized 3:1 to either Durva + Met or Durva alone. Correlative analysis of pre and post TX specimens of primary site was performed for immune cell composition. Digital whole slide images (WSI) were generated using Aperio software to review CD8+ and FoxP3+ T cell counts (CC) and CD8 / FoxP3 ratio from sampled areas in tumor and stromal interface among TX responders (R) and non-responders (NR). Here we review the effect on the immune TME, specifically alterations in T-cell populations.
Results
Pathologic TX response at the primary site was observed in 29.2% of patients (7/24). WSI analysis (n=17) revealed a pre TX mean relative CD8 T cell-FoxP3 T cell distance of 6.1471E-05, that decreased by 49.57% post TX (3.09997E-05). Relative FoxP3+ and CD8+ CC within the tumor and interface also decreased post TX, more pronounced in R compared to NR (Table). Table: 923P
| R (n=6), NR (n=11) | % change after treatment | |
| CD8-FoxP3 Distance/Total Surface Area (SA) | R | -72.13 |
| NR | -33.8 | |
| Interface FoxP3 CC/SA | R | -20.14 |
| NR | -2.16 | |
| Tumor FoxP3 CC/SA | R | -21.26 |
| NR | 8.61 | |
| Interface CD8 CC/SA | R | -11.07 |
| NR | -7.27 | |
| Tumor CD8 CC/SA | R | -25.26 |
| NR | -12.67 |
Conclusions
Interestingly, decreases of both FoxP3+ and CD8+ T cell counts were noted at the interface and tumor after therapy with greater effect in pathologic responders. Understanding alterations in the immune composition of TME is critical for targeted therapy. Further study is warranted to investigate the potential significance of these findings.
Clinical trial identification
NCT03618654; November 1, 2018.
Editorial acknowledgement
Legal entity responsible for the study
Sidney Kimmel Cancer Center at Thomas Jefferson University.
Funding
AstraZeneca.
Disclosure
All authors have declared no conflicts of interest.