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Published on: October 23, 2019
Safety Profile and Adverse Event Management for Futibatinib, An Irreversible FGFR1-4 Inhibitor: Pooled Safety
Funda Meric-Bernstam1, Antoine Hollebecque2, Junji Furuse3
1Department of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, Texas.
Purpose:
Futibatinib, a covalently-binding inhibitor of fibroblast growth factor receptor (FGFR)1-4 gained approval for the treatment of refractory, advanced intrahepatic cholangiocarcinoma (iCCA) harboring an FGFR2 fusion/other rearrangement. An integrated analysis was performed to evaluate safety and provide guidance on the management of futibatinib-associated adverse events (AEs) in patients with unresectable/metastatic tumors, including iCCA.
Patients And Methods:
Data from three global phase I or II studies of futibatinib (NCT02052778; JapicCTI-142552) were pooled. AEs were graded per NCI CTCAE v4.03, where applicable. Safety was analyzed for patients receiving any futibatinib starting dose (overall population) and in those receiving the approved starting dose of 20 mg once every day.
Results:
In total, 469 patients with one of 33 known tumor types were analyzed, including 318 patients who received futibatinib 20 mg every day. AEs of clinical interest (AECI; any grade/grade ≥3) in the overall population included hyperphosphatemia (82%/19%), nail disorders (27%/1%), hepatic AEs (27%/11%), stomatitis (19%/3%), palmar-plantar erythrodysesthesia syndrome (PPES; 13%/3%), rash (9%/0%), retinal disorders (8%/0%), and cataract (4%/1%). Median time to onset of grade ≥3 AECIs ranged from 9 days (hyperphosphatemia) to 125 days (cataract). Grade ≥3 hyperphosphatemia, hepatic AEs, PPES, and nail disorders resolved to grade ≤2 within a median of 7, 7, 8, and 28 days, respectively. Discontinuations due to treatment-related AEs were rare (2%), and no treatment-related deaths occurred. AE management included phosphate-lowering medication and dose adjustments.
Conclusions:
Futibatinib showed a consistent and manageable safety profile across patients with various tumor types. AECIs were mostly reversible with appropriate clinical management.
Insights
Futibatinib, an FGFR inhibitor, demonstrated a manageable safety profile in patients with advanced cancers. Adverse events were largely reversible with appropriate management, supporting its use in treating intrahepatic cholangiocarcinoma.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Futibatinib is an approved FGFR inhibitor for intrahepatic cholangiocarcinoma (iCCA).
- Management of adverse events (AEs) is crucial for patients with unresectable/metastatic tumors.
Purpose of the Study:
- To evaluate the safety profile of futibatinib in a broad patient population.
- To provide guidance on managing futibatinib-associated adverse events.
Main Methods:
- Integrated analysis of data from three global Phase I/II studies.
- Safety analysis included overall population and those receiving the approved 20 mg daily dose.
- Adverse events graded per NCI CTCAE v4.03.
Main Results:
- 469 patients analyzed; 318 received 20 mg daily futibatinib.
- Common AEs included hyperphosphatemia (82%), nail disorders (27%), and hepatic AEs (27%).
- Most AEs were reversible; treatment discontinuation was rare (2%) with no treatment-related deaths.
Conclusions:
- Futibatinib exhibits a consistent and manageable safety profile across diverse tumor types.
- Adverse events of clinical interest were mostly reversible with clinical management.
- AE management strategies include dose adjustments and phosphate-lowering medication.
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