Clinical trial data unveil a driver of FGFR inhibitor response in gastric cancer

Collaborative study published in the journal Cancer Discovery

27 May 2016

Scientists from AstraZeneca’s Oncology Innovative Medicines Unit, the Institute of Cancer Research, London and the Royal Marsden Foundation Trust, recently published the results of a clinical biomarker study in solid tumours. The publication defines a potential driver for clinical responses to fibroblast growth factor receptor inhibitors in gastric cancers.

The fibroblast growth factor receptor family is associated with cell growth, proliferation, differentiation and survival.  It is activated within subsets of most common cancers.

In the past, patients with FGFR gene amplification have responded inconsistently to FGFR inhibitors in early clinical trials. This study questioned why this might be. In order to find the answer, scientists developed a novel imaging platform, which allowed for quantitative assessment of FGFR gene amplification and how this differed across gastric tumours.  By analysing tumours from patients dosed with AZD4547, AstraZeneca’s FGFR tyrosine kinase inhibitor, the team observed that multiple copies of the FGFR gene (known as gene amplification) had to be present in all  tumour cells (known as ‘clonal’) in order to see a positive response.

The prevalence of high and clonal amplification of FGFR in tumours is low, so these observations are crucial in both understanding why previous studies have shown inconsistent response and an approach for selecting the patients that might most likely respond for future clinical trials with FGFR inhibitors.

A new blood based test which detects the FGFR gene in DNA released by the tumour might prove to be of use in directing future treatment, identifying a subset of patients who may benefit from an FGFR inhibitor.

The study findings were published in Cancer Discovery in May 2016. 

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