We performed a screening, or RF Kinase screening where we identified FGFR1, a tyrosine kinase receptor, as a possible mechanism of resistance to CDK4/6 inhibitors. The CDK4/6 inhibitors in combination with endocrine therapy now are the standard treatment for breast cancer patients, oestrogen receptor positive breast cancer patients. We found that when there is overexpression of this receptor FGFR1 the cells in mice, PDX mice, are less sensitive to the CDK4/6 inhibitor treatment. So we went to clinic to analyse some clinical data and we saw that a cohort of 34 patients treated with CDK4/6 inhibitors. We analysed the circulating tumour DNA after progression on this drug and we saw that these patients showed enrichment of FGFR alterations, like FGFR1 amplification, FGFR2 amplification or FGFR1 or 2 activating mutation.
Does this signal it as a targetable pathway for treating that resistance?
Yes, there are different FGFR inhibitors actually in clinical development. We have a clinical study ongoing at Vanderbilt University where we are evaluating the novel combination, a certain treatment anti-oestrogen plus CDK4/6 inhibitor plus or minus FGFR inhibitors. We are using erdafitinib, we are selecting the patients for FGFR alteration, I mean FGFR1, 2, 3 or 4 amplification. If a patient is oestrogen receptor positive, HER2 negative with an FGFR amplification there is the possibility to go in the trial to receive this kind of treatment.
So do you recommend FGFR screening as something which clinicians should be aware of?
Yes, maybe it’s too early to recommend it but different studies are ongoing. For sure different groups are seeing the same that we are seeing in our clinical data - that FGFR1 correlated with resistance. If we are able to confirm this data for sure we have to investigate the FGFR amplification or, maybe better, the FGFR1 overexpression or mutation to decide if these patients could receive a different kind of treatment.
Any forecasts of when those trials might be concluding?
Yes, the clinical trial is ongoing so it’s too early to say something, we have to wait to maybe next year to see some preliminary results.