1492MO - Immune and vascular biomarkers associated with efficacy and mechanism of actions of the combination of lenvatinib (L) and eribulin (E) in leiomyosarcoma (LMS) and liposarcoma (LPS)

Background

The interactions with immune system and influence on the tumor microenvironment (TME) of L + E remain elusive. The LEADER study (NCT03526679) investigated the efficacy of L + E in advanced LMS and LPS and immune-related biomarkers were examined.

Methods

Pre- and post-treatment (2 cycles) samples were analyzed using the nCounter Platform by Nanostring PanCancer Immune Profiling Panel including 760 genes associated with immune cells and regulations. Analyses were based on gene expression levels and immune cells, which was estimated by transcriptomic-based methods (MCP-Counter or Danaher et al. 2017).

Results

32 samples (11 pre-post paired) had adequate quality for analysis; there were 4 and 15 pts, with PR and SD as best response; 13 pts had PFS ≥ 6 months. Based on pretreatment samples, higher endothelial cells were significantly associated with PR (p = 0.027). Bundled pre (n = 19) vs post (n=13)-treatment samples analysis showed a significant increase in dendritic cells after L + E (p = 0.037). In paired samples, patients with PFS longer than 6 months had significantly increased dendritic cells (p = 0.031), Th1 cells (p = 0.031), macrophages (p = 0.016), cytotoxic cells (p = 0.047), and exhausted CD8 (p = 0.047). Results of differential gene expression of paired samples also suggested a similar pattern of transformation into an active immune TME after L +E: mRNA levels of TNFSR14 (p = 0.03) and CCL19 (p = 0.03), both are molecules associated with tertiary lymphoid structure, were significantly increased.

Conclusions

L+E may have the ability to adjust the TME. A pre-treatment immune-suppressive TME was associated with worse clinical efficacy, but pts with a transformed immune-active post-treatment TME after L + E were associated with better outcome.

Clinical trial identification

NCT03526679.

Editorial acknowledgement

Legal entity responsible for the study

T.W-W. Chen.

Funding

National Taiwan University Hospital Clinical Trial Center, Eisai.

Disclosure

T.W-W. Chen: Financial Interests, Personal, Speaker’s Bureau: Eisai; Financial Interests, Personal and Institutional, Research Grant: Eisai. All other authors have declared no conflicts of interest.