24P - Fibroblast growth factor receptor (FGFR) as a target for epigenetic therapies: A case review for a new approach to target tumors with somatic mutations/amplifications of FGFR

Background

Fibroblast growth factor receptors (FGFRs) are aberrantly activated in less than 10 percent of solid tumors, through different mechanisms such as single nucleotide variants, gene fusions and copy number alterations. In some types of cancer, such as urothelial or cholangiocarcinomas this frequency increases to 10–30%. Also, we see increased copy number alterations in breast cancer specifically after using cytotoxic therapies. There have been significant efforts to develop anti-FGFR drugs. Despite initial sensitivity to FGFR inhibition, acquired drug resistance leading to cancer progression develops in most patients.

Methods

Commercial ctDNA assay was provided through Guardant Laboratories. Patients had been informed, consented and treated with multi-targeted epigenetic therapies as on or off label in a phase II clinical trial. The protocol consisted of NP-Q (nanoformulated quercetin) as epigenetic modifier. The detection of ctDNA was correlated with patient’s outcome. All patients were treated with multi-targeted epigenetic therapies on a daily basis per protocol until retested. The retest was performed at least 14 days after the initial testing. Patients did not change their diet or receive any additional therapies during this time.

Results

There was a total of 28 cases identified (7 male and 21 female, ages from 33 to 76), from which 18 cases were tracked and 6 did not desire to be treated and 4 although received therapies, could not be retested. The total responders to the therapy were 14 and non-responders were 4. The response range was between 0.1 mutated allele frequencies to 3.7. Average response was at 2.6. Duration of response was tracked up to 12 months. The range of non-responders increased MAF was not more than 0.2 (3 patients with 0.1 and one patient with 0.2 percent). The response was statistically significant with average of (++) reduction of amplified gene expression manifested by direct inhibition of the FGFR.

Conclusions

To our knowledge this is the first report on longitudinal monitoring of FGFR alteration with liquid biopsy in response to epigenetic therapies. We believe such an approach can be utilized at larger scale to improve patient's response to therapies.

Clinical trial identification

N/A

Editorial acknowledgement

Legal entity responsible for the study

The author.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.