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Poster viewing and lunch

152TiP - Trial in progress: Imatinib to convert triple negative breast cancer into estrogen receptor (ER) positive breast cancer - a window of opportunity trial

Date

12 May 2023

Session

Poster viewing and lunch

Presenters

Barbro Linderholm

Citation

Annals of Oncology (2023) 8 (1suppl_4): 101220-101220. 10.1016/esmoop/esmoop101220

Authors

B.K. Linderholm1, E. Kapocs2, S. Lehn3, K. Pietras4

Author affiliations

  • 1 Sahlgrenska University Hospital - Jubileumskliniken, Göteborg/SE
  • 2 Sahlgrenska University Hospital - Jubileumskliniken, 413 45 - Gothenburg/SE
  • 3 Lund University - Faculty of Medicine, 205 02 - Lund/SE
  • 4 Lund University, SE-223 81 - Lund/SE

Resources

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Abstract 152TiP

Background

A large component of the tumor microenvironment in breast cancer consists of cancer-associated fibroblasts (CAFs), a cell type which can influence tumor progression, angiogenesis and therapy resistance. Receptors on CAF are activated by ligands secreted from tumor cells resulting in establishment of a malignant paracrine crosstalk, supporting the tumor as a whole. Preclinical data suggests a specific role for tumor cell-secreted Platelet-derived growth factor-CC (PDGF-CC) in maintaining the triple-negative breast cancer (TNBC) phenotype through paracrine activation of PDGFR (Platelet-derived growth factor receptor) on CAFs. Inhibition of CAF PDGFR in preclinical TNBC breast tumor models resulted in tumors converting into a luminal ER subtype, with subsequent response to endocrine therapy. Imatinib, a PDGFR inhibitor, was tested in the preclinical setting leading to comparable results. To establish a proof-of-principle concerning if ER expression can be induced in patients, imatinib will be given to TNBC patients before surgery to analyze expression of ER before and after treatment.

Trial design

The study is a window-of-opportunity phase II, single center clinical trial investigating the efficacy and feasibility of short term imatinib (400 mg per day for 10 days) for early TNBC patients planned for surgery, who are not eligible for neoadjuvant chemotherapy. The primary endpoint is to determine changes in ER expression before and after imatinib treatment by analyzing the diagnostic biopsy and the surgical specimen. If ER expression changes from 0% to 2% or more, or ER is changed from 1-9% to either ≥10% or at least 2% increase combined with a significant increase in luminal gene transcripts, the primary endpoint is met. Secondary endpoints include determining safety of short-term imatinib and assessing blood and tissue markers such as ctDNA (circulating tumorDNA), immune cell markers and analyses of activity in luminal gene expression programs. Thirty-five patients will be recruited with an interim analysis planned after recruitment of 20 patients. The study is now open for inclusion.

Clinical trial identification

NCT05722795.

Legal entity responsible for the study

Vastra Gotalandsregionen/Department of Oncology, Gothenburg, Sweden.

Funding

Mats Paulsson Foundation, Cancera Foundation, The Swedish Cancer Society, Göran Grosskopf and Region Skåne ALF.

Disclosure

All authors have declared no conflicts of interest.

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