Measurements of copies of a single gene circulating in the bloodstream allowed scientists to identify patients with stomach cancer who were most likely to respond to treatment. The gene, FGFR2, is needed for continued growth of cancerous cells, and the drug is an FGFR inhibitor.1
High levels of copies of circulating FGFR2 correlated with increased responses to FGFR inhibitor treatment. This blood test could be used to guide treatment by identifying the patients most likely to respond to this particular treatment.
This phase II clinical trial examined the efficacy of the FGFR inhibitor AZ4547 in 341 patients with either stomach or breast cancer. Researchers discovered excessive copies of FGFR2 in tumor biopsies in 9% of tumors from the 135 patients with stomach cancer.
Nine patients with FGFR2 amplification received AZ547, with 3 responding to treatment. The drug elicited responses in those 3 patients for an average of 6.6 months.
Researchers discovered that 18% of patients with breast cancer exhibited an amplified number of copies of FGFR1, a similar gene to FGFR2. These tumors, however, were not susceptible to AZ547 treatment.
Researchers discovered that the discrepancy in responses was due to FGFR2’s function in the cells. FGFR2 can take over the pathways that enable cancer to grow and spread. Some stomach tumors had developed an oncogene addiction phenotype in which high levels of FGFR2 were essential for continued growth.
“Our study has identified a potential new treatment for a subset of patients with gastric cancer, and has explained why some gastric cancers were responding to treatment while others did not. We were able to design a blood test to screen for patients who were most likely to benefit from an FGFR2 inhibitor, helping us to target drug therapy at those patients who were most likely to benefit,” explained Nicholas Turner, MD, team leader in molecular oncology at The Institute of Cancer Research, London, and consultant medical oncologist at The Royal Marsden NHS Foundation Trust, London, United Kingdom, and co-leader of the study.
“The research helps shed light on how tumors can become addicted to certain cancer genes, and shows how we can treat the disease effectively by taking advantage of these weak points in cancer’s armory.”
1. Pearson A, Smyth E, Babina IS, et al. High-level clonal FGFR amplification and response to FGFR inhibition in a translational clinical trial [published online May 13, 2016]. Cancer Discov. doi:10.1158/2159-8290.CD-15-1246.