Often, fibroblast growth factor receptor (FGFR) 2 gene alterations occur in the pathogenesis of cholangiocarcinoma. The FDA recently approved an oral inhibitor of FGFR2, pemigatinib (PemazyreTM, Incyte Corporation), which has shown efficacy in patients with previously treated, locally advanced, or metastatic cholangiocarcinoma with and without FGFR2 gene alterations. FoundationOne®CDx was also approved as a companion diagnostic test for this indication.
FDA approval was based on a clinical trial that enrolled 146 patients with disease progression following at least one previous treatment for cholangiocarcinoma. Patients were separated into one of three groups: those with FGFR2 fusions or rearrangements, those with other FGF/FGFR alterations, or those with no FGF/FGFR alterations. All participants received 13.5 mg of oral pemigatinib once daily for a 21-day cycle, with 2 weeks on and 1 week off. Treatment was stopped if disease progression, unacceptable toxicity, withdrawal of consent, or physician recommendation to do so occurred.
After a median follow-up of 17.8 months, 35.5% of patients with FGFR2 gene alterations reached an objective response—three complete responses and 35 partial responses. The most common treatment-related adverse event was hyperphosphatemia, which occurred in 60% of patients. Grade 3 or worse adverse events occurred in 64% of patients and included arthralgia (6%), stomatitis (5%), hyponatremia (5%), abdominal pain (5%), and fatigue (5%).
"This approval demonstrates that while we continue to focus our efforts on addressing the COVID-19 pandemic, the FDA remains committed to the important work of reviewing treatments for patients with cancer and other serious conditions," stated Richard Pazdur, MD, Director of the FDA's Oncology Center of Excellence and Acting Director of the Office of Oncologic Diseases in the FDA's Center for Drug Evaluation and Research. "With [pemigatinib], we considered the observed efficacy results to be clinically meaningful and the overall risk to benefit assessment for patients with tumors harboring FGFR2 gene fusions and other rearrangements to be favorable, particularly when we considered that these patients have no other good options following first line treatment with chemotherapy."
For More Information
Abou-Alfa G, Sahai V, Hollebecque A, et al (2020). Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicenter, open-label, phase 2 study. Lancet Oncol. [Epub ahead of print] DOI:101016/S1470-2045(20)30109-1
Clinicaltrials.gov (2020). Efficacy and safety of pemigatinib in subjects with advanced/metastatic or surgically unresectable cholangiocarcinoma who failed previous therapy (FIGHT-202). NLM Identifier: NCT02924376
Pemazyre™ (pemigatinib) prescribing information (2020). Incyte Corporation. Available at: https://www.pemazyre.com/?utm_source=google&utm_medium=cpc&utm_campaign=Branded_Pemazyre_DTC_Exact_%3BS%3BPH%3BBR%3BONC%3BDTC%3BBR&utm_content=General_Pemazyre_E&utm_term=pemigatinib&gclid=CjwKCAjwkPX0BRBKEiwA7THxiI4_y9zMR5CsRj_1nHH6aq9qtI1w4DyDgkE9p5VPR4C2_YgIvkuxzBoCGFkQAvD_BwE&gclsrc=aw.ds
Image Courtesy of Nephron. Licensed under CC BY-SA 3.0