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Outcomes following FGFR Inhibitor Therapy in Patients with Cholangiocarcinoma
Jennifer J Gile1, Vanessa Wookey1, Tyler J Zemla2
1Department of Oncology, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA.
Background:
Sequencing efforts in patients with cholangiocarcinoma (CCA) have provided insights into molecular mechanisms including fibroblast growth factor receptor (FGFR) alterations. There is a lack of data on outcomes of patients following cessation of FGFR inhibitor (FGFRi) therapy.
Objective:
We describe the clinical outcomes following initial FGFRi treatment in CCA harboring FGFR alterations.
Patients And Methods:
We conducted a multicentric, retrospective analysis of patients with FGFR-altered CCA diagnosed between 2010 and 2021. Median overall survival (OS) and progression-free survival (PFS) analyses were performed using the Kaplan-Meier method.
Results:
We identified 88 advanced or metastatic CCA patients, 28 males (31.8%) and 60 females (68.2%), harboring FGFR alterations who received FGFRi. Median PFS on initial FGFRi was 6.6 months (95% confidence interval (CI): 5.5-8.3). Following cessation of first FGFRi therapy, 55% patients received systemic therapy as next line: 67% received chemotherapy or targeted treatment and 33% received another FGFRi. Median PFS for patients who received chemotherapy or targeted agent was 2.1 months (95% CI 1.6-5.7) and for patients who received a second FGFRi was 3.7 months (95% CI 1.5-not evaluable). OS was 2.0 months for patients who did not receive any therapy compared to 8.7 months with chemotherapy and 8.6 months with another FGFRi. In addition, one patient treated with pemigatinib developed FGFR2 M540_I541insMM alteration at time of resistance, which has not been functionally characterized and its effect on protein function remains unknown.
Conclusions:
Understanding the mechanisms of resistance with FGFRi is essential to understand sequencing of treatments. In this study, patients received standard chemotherapy in the first line and were fit enough to be considered for subsequent therapy with an FGFRi. Almost half of the patients become ineligible to receive further systemic therapy following progression on FGFRi. As more agents are being introduced, detailed understanding of outcomes following treatment with an FGFRi, including subsequent FGFRi, is essential.
Insights
Outcomes after fibroblast growth factor receptor inhibitor (FGFRi) therapy in cholangiocarcinoma (CCA) patients are limited. This study shows that subsequent chemotherapy or FGFRi offers improved survival compared to no further treatment after initial FGFRi cessation.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Cholangiocarcinoma (CCA) sequencing reveals fibroblast growth factor receptor (FGFR) alterations.
- Limited data exists on patient outcomes after FGFR inhibitor (FGFRi) therapy cessation.
Purpose of the Study:
- To describe clinical outcomes in CCA patients with FGFR alterations following initial FGFR inhibitor (FGFRi) treatment.
Main Methods:
- Multicentric, retrospective analysis of 88 advanced/metastatic CCA patients with FGFR alterations (2010-2021).
- Kaplan-Meier method used for overall survival (OS) and progression-free survival (PFS) analyses.
Main Results:
- Median PFS on initial FGFRi was 6.6 months.
- Following FGFRi cessation, 55% received subsequent systemic therapy (chemotherapy, targeted treatment, or another FGFRi).
- Median PFS was 2.1 months with chemotherapy/targeted agents and 3.7 months with a second FGFRi. OS was 8.7 months with chemotherapy and 8.6 months with a second FGFRi, versus 2.0 months without further therapy.
Conclusions:
- Understanding FGFR inhibitor resistance mechanisms is crucial for treatment sequencing in CCA.
- Nearly half of patients become ineligible for further therapy after FGFRi progression.
- Detailed outcomes following FGFRi, including subsequent FGFRi use, are essential as new agents emerge.
