Targeting the PDGF receptor in soft tissue sarcomas: Understanding, combining and monitoring

Host: Winette van der Graaf, The Institute of Cancer Research, UK


Room: Room 12

The PDGF-alpha receptor increasingly gets a lot of attention in soft tissue sarcoma since the remarkable results of a randomised phase 2 study combining olaratumab, a PDGFR-alpha antibody, with doxorubicin versus the golden standard doxorubicin, showing a median overall survival benefit of 11.8 months. The mechanism of action of this novel combination still needs to be sorted, stromal reactions may play a role. Recent in vitro studies have shown that combinations of PDGFRa/b receptor inhibitors with other tyrosinekinase inhibitors may confer resistant in sarcomas. Finally, therapeutic drug monitoring can lead to better exposure to drugs targeting PDGFR and other tyrosine kinases in vivo.

Participants will learn from different perspectives -from bench to bedside- about the effect of blocking PDGFR and other receptors in sarcomas. Olaratumab in combination with doxorubicin has the potential to become a new standard treatment in the metastatic setting, which will greatly impact the sarcoma clinic of the future. Blockade of PDGFR receptors, either alone or in combination can confer drug resistance. Lastly, the participants will get a better understanding of the challenges of keeping patients on adequate doses of PDGFR targeting tyrosine kinase inhibitors to get optimal exposure. Ways to reduce drug or food interactions that make PDGFR receptor tyrosine kinase inhibitors less effective will be discussed.

Confirmed speakers:
Paul Huang, The Institute of Cancer Research, London, UK
Nielka van Erp, Radboud Institute for Health Sciences, The Netherlands
Andrew J. Wagner, Harvard Medical School and Dana-Farber Cancer Institute, USA

Defining the mechanisms and biomarkers of PDGFR inhibitor resistance and response