TAT 2020: Predictive Biomarker for FGFR Inhibitors in Breast Cancer
Posted: Wednesday, March 25, 2020
Fibroblast growth factor receptor (FGFR) 1-4 high mRNA expression appears to be a predictive biomarker for effectiveness of FGFR inhibitors, such as rogaratinib, according to an exploratory study originally intended to be presented at the European Society for Medical Oncology (ESMO) Targeted Anticancer Therapies (TAT) Congress 2020 (Abstract 29P). However, this association was not seen with multityrosine kinase inhibitors, such as lucitanib, in breast cancer patient-derived xenografts. “Multityrosine kinase inhibitor efficacy does not rely on high mRNA expression levels of its targets in breast cancer,” stated Cinta Hierro Carbó, MD, MSc, of Catalan Institute of Oncology, Badalona, Spain.
The researchers tested the efficacy of rogaratinib in 17 models of FGFR1-amplified breast cancer patient-derived xenografts and lucitanib in 7 FGFR1-amplified xenografts. They found that FGFR1-4 high mRNA expression had a stronger correlation with efficacy to FGFR inhibitors compared with FGFR copy number alterations. However, in patient-derived xenografts with low FGFR1-4 mRNA levels, multityrosine kinase inhibitors demonstrated higher antitumor activity than FGFR inhibitors.
Interestingly, some sensitive FGFR1-amplified patient-derived xenografts expressed low FGFR1 mRNA expression levels but high FGFR2-4 mRNA levels. Of three patients identified by Dr. Carbó and colleagues who achieved prolonged responses of 14 to 50 months, just one had FGFR1-high mRNA expression. Also, two patients who had previously received an FGFR inhibitor achieved clinical benefit with a multityrosine kinase inhibitor. The mRNA expression levels of other angiogenic targets, including vascular endothelial growth factor receptor 1 to 3 or platelet-derived growth factor receptor alpha/beta and their ligands, did not appear to correlate with multityrosine kinase inhibitor sensitivity.
Disclosure: The study authors’ disclosure information can be found at www.esmo.org.