Sameek Roychowdhury, MD, PhD, medical oncologist, assistant professor, the Department of Internal Medicine and the Department of Pharmacology, The Ohio State University, discusses the prevalence of 

 mutations in intrahepatic cholangiocarcinoma (ICC).

 mutations, which activate the FGFR receptor and cause abnormal signaling that affects cell growth, are most common in ICC, plus urothelial or bladder cancers, Roychowdhury says. Specifically, 

 mutations tend to be more common in ICC, ranging from 10% to 15% of patients in that subset, Roychowdhury adds. However, 

 mutations are more common in bladder cancer, appearing in 15% to 20% of that subset of patients, Roychowdhury explains.

 point mutations tend to occur more often in bladder cancer, whereas in ICC, 

 gene fusions or rearrangements are typical, Roychowdhury continues. Despite these tendencies, a variety of 

 mutations can present in these cancers, Roychowdhury concludes.

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Sameek Roychowdhury, MD, PhD, discusses the prevalence of FGFR mutations in intrahepatic cholangiocarcinoma.

Dr. Roychowdhury on FGFR Mutations in Intrahepatic Cholangiocarcinoma

Sameek Roychowdhury, MD, PhD, medical oncologist, assistant professor, department of Internal Medicine, department of Pharmacology, The Ohio State University, discusses future research directions with FGFR inhibitors in patients with cholangiocarcinoma.

In a single-arm, phase 2 study (NCT02150967), investigators evaluated infigratinib (Truseltiq) in previously treated patients with advanced or metastatic cholangiocarcinoma. Future research efforts in this area should focus on getting patients who have received a standard-of-care FGFR inhibitor, such as infigratinib or pemigatinib (Pemazyre), enrolled on clinical trials that are examining second-generation FGFR inhibitors, according to Roychowdhury. Having more patients enrolled to these studies will help to advance the potential development of new therapeutic options for a population with high rates of disease progression, Roychowdhury explains.

The number of patients that can be enrolled in these trials is small because cholangiocarcinoma is a rare malignancy, Roychowdhury adds. As such, collaboration will be necessary to get patients enrolled to these trials and to improve upon the standard of care in this population, Roychowdhury concludes.

Sameek Roychowdhury, MD, PhD, discusses future research directions with FGFR inhibitors in patients with cholangiocarcinoma.

Dr. Roychowdhury on Future Research Directions With FGFR Inhibitors in Cholangiocarcinoma 

Sameek Roychowdhury, MD, PhD, associate professor of medical oncology, the Ohio State University Comprehensive Cancer Center, discusses a phase II study with infigratinib (BGJ398) in patients with cholangiocarcinoma.

Infigratinib (BGJ398) is a selective FGFR inhibitor under investigation in the space, says Roychowdhury. With pre-treatment and post-progression biopsy, investigators have been able to look at acquired mechanisms of resistance in patients with cholangiocarcinoma. Melanie Krook, a postdoctoral researcher with a focus on FGFR drug resistance, was able to demonstrate that the acquisition of new mutations in FGFR did not confer resistance to infigratinib.

In a poster presentation at the 2019 AACR Annual Meeting, Krook explained how she was able to examine protein data as well as in cells that had been transfected with these mutations. Investigators could see that activation of other pathways could render cells sensitive to combination with infigratinib plus either an MTOR or AKT inhibitor. Roychowdhury says that combination therapy could be a potential avenue to pursue down the road after clinical studies exploring the use of single-agent therapies conclude.

The next step for this research is to pool the data from this study and others to gain a better understanding of the overall landscape of FGFR resistance among patients with cholangiocarcinoma. What are all of the mechanisms that can be catalogued? According to Roychowdhury, this information will help inform drug development.

Sameek Roychowdhury, MD, PhD, associate professor of medical oncology, the Ohio State University Comprehensive Cancer Center, discusses a phase II study with infigratinib (BGJ398) in patients with cholangiocarcinoma.
 

Sameek Roychowdhury, MD, PhD

Articles

Dr. Roychowdhury on FGFR Mutations in Intrahepatic Cholangiocarcinoma

Dr. Roychowdhury on Future Research Directions With FGFR Inhibitors in Cholangiocarcinoma

Dr. Roychowdhury on FGFR Inhibitor Infigratinib in Cholangiocarcinoma