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Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label,
Ghassan K Abou-Alfa1, Vaibhav Sahai2, Antoine Hollebecque3
1Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Medical College, Cornell University, New York, NY, USA.
Background:
Fibroblast growth factor receptor (FGFR) 2 gene alterations are involved in the pathogenesis of cholangiocarcinoma. Pemigatinib is a selective, potent, oral inhibitor of FGFR1, 2, and 3. This study evaluated the safety and antitumour activity of pemigatinib in patients with previously treated, locally advanced or metastatic cholangiocarcinoma with and without FGFR2 fusions or rearrangements.
Methods:
In this multicentre, open-label, single-arm, multicohort, phase 2 study (FIGHT-202), patients aged 18 years or older with disease progression following at least one previous treatment and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 recruited from 146 academic or community-based sites in the USA, Europe, the Middle East, and Asia were assigned to one of three cohorts: patients with FGFR2 fusions or rearrangements, patients with other FGF/FGFR alterations, or patients with no FGF/FGFR alterations. All enrolled patients received a starting dose of 13·5 mg oral pemigatinib once daily (21-day cycle; 2 weeks on, 1 week off) until disease progression, unacceptable toxicity, withdrawal of consent, or physician decision. The primary endpoint was the proportion of patients who achieved an objective response among those with FGFR2 fusions or rearrangements, assessed centrally in all patients who received at least one dose of pemigatinib. This study is registered with ClinicalTrials.gov, NCT02924376, and enrolment is completed.
Findings:
Between Jan 17, 2017, and March 22, 2019, 146 patients were enrolled: 107 with FGFR2 fusions or rearrangements, 20 with other FGF/FGFR alterations, 18 with no FGF/FGFR alterations, and one with an undetermined FGF/FGFR alteration. The median follow-up was 17·8 months (IQR 11·6-21·3). 38 (35·5% [95% CI 26·5-45·4]) patients with FGFR2 fusions or rearrangements achieved an objective response (three complete responses and 35 partial responses). Overall, hyperphosphataemia was the most common all-grade adverse event irrespective of cause (88 [60%] of 146 patients). 93 (64%) patients had a grade 3 or worse adverse event (irrespective of cause); the most frequent were hypophosphataemia (18 [12%]), arthralgia (nine [6%]), stomatitis (eight [5%]), hyponatraemia (eight [5%]), abdominal pain (seven [5%]), and fatigue (seven [5%]). 65 (45%) patients had serious adverse events; the most frequent were abdominal pain (seven [5%]), pyrexia (seven [5%]), cholangitis (five [3%]), and pleural effusion (five [3%]). Overall, 71 (49%) patients died during the study, most frequently because of disease progression (61 [42%]); no deaths were deemed to be treatment related.
Interpretation:
These data support the therapeutic potential of pemigatinib in previously treated patients with cholangiocarcinoma who have FGFR2 fusions or rearrangements.
Funding:
Incyte Corporation.
Insights
Pemigatinib showed significant anti-tumour activity in patients with previously treated cholangiocarcinoma harboring Fibroblast growth factor receptor (FGFR) 2 gene alterations. This targeted therapy offers a potential new treatment option for this patient population.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Fibroblast growth factor receptor (FGFR) 2 gene alterations are implicated in cholangiocarcinoma development.
- Pemigatinib is an oral inhibitor targeting FGFR1, 2, and 3.
Purpose of the Study:
- To evaluate the safety and anti-tumour activity of pemigatinib.
- To assess pemigatinib in patients with previously treated, advanced or metastatic cholangiocarcinoma.
- To investigate efficacy in patients with and without FGFR2 fusions or rearrangements.
Main Methods:
- A multicentre, open-label, single-arm, phase 2 study (FIGHT-202).
- 146 patients received 13.5 mg oral pemigatinib daily until disease progression or unacceptable toxicity.
- Patients were stratified into cohorts based on FGF/FGFR alterations.
Main Results:
- Objective response in 35.5% of patients with FGFR2 fusions or rearrangements (3 complete, 35 partial responses).
- Most common adverse event was hyperphosphatemia (60%).
- Grade 3 or worse adverse events occurred in 64% of patients; hypophosphatemia and arthralgia were most frequent.
Conclusions:
- Pemigatinib demonstrates therapeutic potential in previously treated cholangiocarcinoma patients with FGFR2 fusions or rearrangements.
- The safety profile is manageable, with hyperphosphatemia being a notable side effect.
- Further investigation may support pemigatinib as a targeted therapy for this specific cholangiocarcinoma subtype.
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