In the treatment of cholangiocarcinoma, many clinicians may be unaware of the importance of the major oncogenic mutations and other alterations that can be identified and targeted, according to a survey of oncologists presented at the 2021 Gastrointestinal Cancers Symposium.1
“Recent developments and approvals have led to changing paradigms, incorporating the use of targeted therapies for patients with advanced disease. Given the need for a greater understanding of the molecular alterations, varying targets, and available and emerging therapies, more education is needed,” said Kinjal Parikh, PharmD, BCOP, Associate Director of Clinical Strategy for Hematology/Oncology at Medscape Oncology, New York.
Kinjal Parikh, PharmD, BCOP
Arndt Vogel, MD
Dr. Parikh’s conclusion was drawn from a CME-certified clinical practice assessment, authored by Arndt Vogel, MD, of Hanover Medical School, Germany. The assessment identified gaps in knowledge, competence, and confidence regarding testing for mutations and using targeted therapies for patients with unresectable cholangiocarcinoma.
Recently, mutations in isocitrate dehydrogenase isoform 1 (IDH1) and fusions/rearrangements of the fibroblast growth factor receptor 2 (FGFR2) gene have been found to drive many cases of cholangiocarcinoma. Drugs that can target these alterations are becoming available.
Survey of Clinicians
Dr. Parikh and colleagues presented the results of a survey of oncologists. The activity included 25 multiple-choice questions designed to measure knowledge and assess competence, confidence, and attitudes of oncologists about the evidence for and role of molecular testing in unresectable cholangiocarcinoma. The self-assessment survey was made available online to physicians as a learning tool to gain foundational knowledge, as well as to receive feedback about their performance as compared to other test-takers.
A total of 1,009 learners, including 758 physicians, participated in the activity. Of the 104 oncologists, 61% practiced in the community setting, and 70% saw patients with a range of cancers. Slightly more than half reported seeing three to five patients per month with cholangiocarcinoma, whereas one-quarter reported seeing such patients less than once a month.
Lack of Confidence, More to Learn
More than 50% of respondents said they lacked confidence about recognizing targets for cholangiocarcinoma and using targeted treatments. Although 21% said they do not use next-generation sequencing and biomarkers, 32% reported using this technology in patients with progressive disease. Some 35% did not realize that not all panels detect FGFR2 fusions/rearrangements, Dr. Parikh reported.
A total of 29% said they test for IDH mutations, but 60% were familiar with its incidence in cholangiocarcinoma. A number of oncologists were also familiar with some of the clinical trial data for IDH1 inhibitors. For the IDH1 inhibitor ivosidenib, 34% knew the eligibility for the ClarIDHy trial, 51% knew the drug provided a progression-free survival benefit, and 55% recognized that diarrhea and cough were the most common side effects.
As for FGFR2, 56% said they test for this genetic alteration, and 30% knew that three agents are currently being evaluated for FGFR2 fusions/translocations in the first-line setting. About 45% could identify the biomarker eligibility for pemigatinib in the FIGHT-202 trial, and 9% knew the overall survival outcomes; 30% recognized that the most common grade ≥ 3 adverse event with this agent is hypophosphatemia.
Slightly more than half (55%) also recognized that HER2 gene alterations occur at a rate of 5% to 8% in cholangiocarcinoma. However, 62% incorrectly identified drugs targeting the vascular endothelial growth factor (VEGF) as promising novel agents with antitumor activity as single agents.
“Precision medicine will continue to be an important component of cancer care in the years to come. Education on targets, testing, and treatments will remain essential to equip oncologists with the insights and resources to give patients with cholangiocarcinoma the best possible outcomes,” Dr. Parikh commented.
DISCLOSURE: The study was funded by Incyte Corporation. Dr. Parikh reported no conflicts of interest. Dr. Vogel has received honoraria from Amgen, Bristol Myers Squibb, Delcath Systems, Ipsen, Janssen, Lilly, MSD, Novartis, Pierre Fabre, Roche, and Sanofi; served as a consultant or advisor to Amgen, AstraZeneca, Baxalta, Bayer, BTG, Eisai, Ipsen, Lilly, Novartis, Pierre Fabre, and Roche; received research funding from Novartis; and received reimbursement for travel, accommodations, and expenses from Bayer, Ipsen, and Roche.
1. Parikh K, Cameron DR, Abair T, et al: Targeted therapies in cholangiocarcinoma: Assessment of US oncologist practice patterns. 2021 Gastrointestinal Cancers Symposium. Abstract 347. Presented January 15, 2021.