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A drug safety evaluation of pemigatinib for advanced cholangiocarcinoma
Pedro Luiz Serrano Uson1,2, Jeremiah Bearss1, Hani M Babiker3
1Mayo Clinic Cancer Center, Mayo Clinic, Phoenix, AZ, USA.
Introduction:
Pemigatinib is a selective small-molecule inhibitor of the fibroblast growth factor receptor (FGFR) 1-3. FGFR is associated with increased cell division, proliferation, and survival. Inhibition of this receptor is an effective treatment against tumors driven by activated fusions in FGFR2.
Areas Covered:
The drug was first evaluated in patients with advanced solid tumors and demonstrated a manageable safety profile, with the most common adverse events being oscillations in blood phosphate levels, fatigue, gastrointestinal symptoms, and skin and ocular toxicities. Pemigatinib was further evaluated in a phase II cohort study of patients with previously treated locally advanced or metastatic cholangiocarcinoma harboring FGFR2 genomic alterations. After a median follow-up of 17.8 months, the objective response rate in patients with tumors harboring FGFR2 fusions or rearrangements was 35.5% (95% CI, 26.5-45.4). Based on these results, the FDA granted accelerated approval on 17 April 2020, to pemigatinib, for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with an FGFR2 fusion or another rearrangement. Articles selected for this review were based on reported studies indexed in PubMed (2010-2023).
Expert Opinion:
Future perspectives in the treatment of FGFR2 fused cholangiocarcinoma include the evaluation of pemigatinib in previously untreated patients and possible active combinations or sequencing strategies with other drugs.
Insights
Pemigatinib effectively treats advanced cholangiocarcinoma with FGFR2 fusions. This targeted therapy showed a 35.5% response rate, leading to FDA accelerated approval for previously treated patients.
Area of Science:
- Oncology
- Pharmacology
- Genomics
Background:
- Fibroblast growth factor receptor (FGFR) signaling promotes tumor cell division, proliferation, and survival.
- Aberrant FGFR2 fusions or rearrangements drive cholangiocarcinoma growth.
- Targeting FGFR offers a therapeutic strategy for specific cancer types.
Purpose of the Study:
- To review the efficacy and safety of pemigatinib in cholangiocarcinoma.
- To summarize clinical trial data for pemigatinib in FGFR2-altered tumors.
- To discuss future treatment perspectives for cholangiocarcinoma.
Main Methods:
- Systematic review of studies indexed in PubMed (2010-2023).
- Analysis of Phase II clinical trial data for pemigatinib in cholangiocarcinoma.
- Evaluation of safety profile and objective response rates.
Main Results:
- Pemigatinib demonstrated a manageable safety profile with common toxicities including phosphate level changes, fatigue, GI, skin, and ocular issues.
- In a Phase II study, pemigatinib achieved an objective response rate of 35.5% in patients with FGFR2 fusions/rearrangements.
- The U.S. Food and Drug Administration (FDA) granted accelerated approval for pemigatinib in April 2020.
Conclusions:
- Pemigatinib is an effective targeted therapy for previously treated, advanced cholangiocarcinoma with FGFR2 alterations.
- Further research will explore pemigatinib in treatment-naive patients and combination strategies.
- Targeted inhibition of FGFR2 fusions represents a significant advancement in cholangiocarcinoma treatment.
