FGFR abnormalities have been reported in many cancers, including breast, lung, and bladder cancers. While the types of events that occur in these cancers are different, preclinical evidence supports a role for oncogenesis in each of these types,” said formal discussant of the FGFR inhibitor studies presented at the American Association for Cancer Research Annual Meeting, Paul K. Paik, MD, of Memorial Sloan Kettering Cancer Center, New York. “However, there is not a 100% correlation in preclinical models between response to FGFR inhibitors and FGFR abnormalities.”
Both abstracts showed that the respective drugs have good selectivity and potency as kinase inhibitors, and both study designs were similar, Dr. Paik said.
“Overall, these studies provide an early signal of promising activity in bladder cancer and outlier activity in lung and breast cancer,” Dr. Paik said.
These are early data, he emphasized, and there are several outstanding issues related to response, including whether FGFR amplification alone is a sufficient driver event, whether drug concentration sufficient for FGFR1 inhibition in the amplified setting is being attained, and whether there is a role for ligand binding inhibition or alternative pathway activation.
“Mutation and fusion events appear to have a higher predictive value, and gene amplification less so. Future research will tell us more about these compounds and the subtleties involved in targeting them,” Dr. Paik said. ■
Disclosure: Dr. Paik has received research funding from AstraZeneca and GlaxoSmithKline.
Fibroblast growth factor receptor (FGFR) inhibitors are an emerging area of interest in cancer therapeutics. Studies presented at the 2014 American Association for Cancer Research (AACR) Annual Meeting in San Diego provided early encouraging data for two investigational pan-FGFR inhibitors for the...