33P - Serological assessment of extracellular matrix (ECM) remodeling in relation to clinical response in metastatic melanoma patients treated with Ipili...

Date 08 December 2017
Event ESMO Immuno-Oncology Congress 2017
Session Lunch & Poster Display session
Topics Central Nervous System Malignancies
Presenter Christina Jensen
Citation Annals of Oncology (2017) 28 (suppl_11): xi6-xi29. 10.1093/annonc/mdx711
Authors C. Jensen1, D.H. Madsen2, M. Hansen2, H. Schmidt3, I. Svane2, M.A. Karsdal1, N. Willumsen1
  • 1Biomarkers & Research, Nordic Bioscience A/S, 2730 - Herlev/DK
  • 2Center For Cancer Immune Therapy, Herlev Hospital, University of Copenhagen, 2730 - Herlev/DK
  • 3Department Of Oncology, Aarhus University Hospital, 8000 - Aarhus C/DK

Abstract

Background

The checkpoint inhibitor Ipilimumab induces long-lasting clinical responses in a proportion of patients with metastatic melanoma. However, most patients do not benefit from therapy. A desmoplastic stroma (tumour fibrosis), characterized by excessive extracellular matrix (ECM) remodeling, can result in reduced drug delivery and T-cell infiltration into the tumour and has been associated with poor prognosis and lack of therapy response. Here we address non-invasive biomarkers reflecting ECM remodeling in the tumour microenvironment, for associations with clinical response to Ipilimumab in patients with metastatic melanoma.

Methods

Serum biomarkers of collagen type III formation (Pro-C3), MMP-degraded type I collagen (C1M) and MMP-degraded type IV collagen (C4M) were studied with competitive ELISAs in pretreatment serum from 66 patients with metastatic melanoma. Results were correlated with objective response rate (ORR) and survival outcomes (OS) by univariate Cox analysis and Kaplan Meier plots.

Results

Pro-C3, C1M and C4M were significantly elevated in patients with progressive disease (PD) compared to the combined group of patients with stable disease (SD), partial response (PR) and complete response (CR) at baseline. Moreover, in the subgroup of patients with baseline biomarker levels higher than the 75th percentile (Q4), only 6-13% responded (CR+PR+SD) compared to 46-48% in the group of patients with low biomarker levels (Q1-Q3). The median OS was 285, 161 or 198 days in biomarker high patients versus 596, 592 or 621 days in biomarker low patients for Pro-C3 (HR 2.13, 95%CI 1.12-4.04), C1M (HR 1.70, 95%CI 0.85-3.38) and C4M (HR 2.43, 95%CI 1.26-4.70), respectively.

Conclusions

High baseline levels of Pro-C3, C1M and C4M were associated with progressive disease and decreased overall survival in metastatic melanoma patients receiving Ipilimumab. This suggest the ECM biomarkers ability to predict response to checkpoint inhibitors at baseline. Future studies are needed to investigate the biomarkers applicability in other types of immunotherapies and cancers.

Clinical trial identification

Legal entity responsible for the study

Nordic Bioscience

Funding

None

Disclosure

C. Jensen, M.A. Karsdal, N. Willumsen: Employee of Nordic Bioscience involved in biomarker development.

All other authors have declared no conflicts of interest.