An open-label study of pemigatinib in cholangiocarcinoma: final results from FIGHT-202☆

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Abstract

Background

Fibroblast growth factor receptor 2 ( FGFR2) fusions and rearrangements are clinically actionable genomic alterations in cholangiocarcinoma (CCA). Pemigatinib is a selective, potent, oral inhibitor of FGFR1-3 and demonstrated efficacy in patients with previously treated, advanced/metastatic CCA with FGFR2 alterations in FIGHT-202 (NCT02924376). We report final outcomes from the extended follow-up period.

Patients and methods

The multicenter, open-label, single-arm, phase II FIGHT-202 study enrolled patients ≥18 years old with previously treated advanced/metastatic CCA with FGFR2 fusions or rearrangements (cohort A), other FGF/ FGFR alterations (cohort B), or no FGF/ FGFR alterations (cohort C). Patients received once-daily oral pemigatinib 13.5 mg in 21-day cycles (2 weeks on, 1 week off) until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) in cohort A assessed as per RECIST v1.1 by an independent review committee; secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.

Results

FIGHT-202 enrolled 147 patients (cohort A, 108; cohort B, 20; cohort C, 17; unconfirmed FGF/ FGFR alterations, 2). By final analysis, 145 (98.6%) had discontinued treatment due to progressive disease (71.4%), withdrawal by patient (8.2%), or adverse events (AEs; 6.8%). Median follow-up was 45.4 months. The ORR in cohort A was 37.0% (95% confidence interval 27.9% to 46.9%); complete and partial responses were observed in 3 and 37 patients, respectively. Median DOR was 9.1 (6.0-14.5) months; median PFS and OS were 7.0 (6.1-10.5) months and 17.5 (14.4-22.9) months, respectively. The most common treatment-emergent AEs (TEAEs) were hyperphosphatemia (58.5%), alopecia (49.7%), and diarrhea (47.6%). Overall, 15 (10.2%) patients experienced TEAEs leading to pemigatinib discontinuation; intestinal obstruction and acute kidney injury ( n = 2 each) occurred most frequently.

Conclusions

Pemigatinib demonstrated durable response and prolonged OS with manageable AEs in patients with previously treated, advanced/metastatic CCA with FGFR2 alterations in the extended follow-up period of FIGHT-202.

Highlights

•

FIGHT-202 evaluated pemigatinib in patients with previously treated, advanced/metastatic CCA with FGFR2 rearrangements.
•

Median follow-up was 45.4 months; pemigatinib demonstrated an ORR of 37% and a median DOR of 9.1 months.
•

Median PFS and OS were 7.0 and 17.5 months, respectively.
•

AEs with pemigatinib treatment were manageable; during extended follow-up, no new safety signals were identified.
•

The importance of tumor molecular profiling and pemigatinib efficacy in CCA with FGFR2 fusions/rearrangements are described.

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Most cited references 39

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Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer.

Juan Ignacio Valle, Harpreet Singh Wasan, Daniel H Palmer … (2010)

There is no established standard chemotherapy for patients with locally advanced or metastatic biliary tract cancer. We initially conducted a randomized, phase 2 study involving 86 patients to compare cisplatin plus gemcitabine with gemcitabine alone. After we found an improvement in progression-free survival, the trial was extended to the phase 3 trial reported here. We randomly assigned 410 patients with locally advanced or metastatic cholangiocarcinoma, gallbladder cancer, or ampullary cancer to receive either cisplatin (25 mg per square meter of body-surface area) followed by gemcitabine (1000 mg per square meter on days 1 and 8, every 3 weeks for eight cycles) or gemcitabine alone (1000 mg per square meter on days 1, 8, and 15, every 4 weeks for six cycles) for up to 24 weeks. The primary end point was overall survival. After a median follow-up of 8.2 months and 327 deaths, the median overall survival was 11.7 months among the 204 patients in the cisplatin-gemcitabine group and 8.1 months among the 206 patients in the gemcitabine group (hazard ratio, 0.64; 95% confidence interval, 0.52 to 0.80; P<0.001). The median progression-free survival was 8.0 months in the cisplatin-gemcitabine group and 5.0 months in the gemcitabine-only group (P<0.001). In addition, the rate of tumor control among patients in the cisplatin-gemcitabine group was significantly increased (81.4% vs. 71.8%, P=0.049). Adverse events were similar in the two groups, with the exception of more neutropenia in the cisplatin-gemcitabine group; the number of neutropenia-associated infections was similar in the two groups. As compared with gemcitabine alone, cisplatin plus gemcitabine was associated with a significant survival advantage without the addition of substantial toxicity. Cisplatin plus gemcitabine is an appropriate option for the treatment of patients with advanced biliary cancer. (ClinicalTrials.gov number, NCT00262769.) 2010 Massachusetts Medical Society

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Cholangiocarcinoma 2020: the next horizon in mechanisms and management

Jesus Banales, Jose Marin, Angela Lamarca … (2020)

Cholangiocarcinoma (CCA) includes a cluster of highly heterogeneous biliary malignant tumours that can arise at any point of the biliary tree. Their incidence is increasing globally, currently accounting for ~15% of all primary liver cancers and ~3% of gastrointestinal malignancies. The silent presentation of these tumours combined with their highly aggressive nature and refractoriness to chemotherapy contribute to their alarming mortality, representing ~2% of all cancer-related deaths worldwide yearly. The current diagnosis of CCA by non-invasive approaches is not accurate enough, and histological confirmation is necessary. Furthermore, the high heterogeneity of CCAs at the genomic, epigenetic and molecular levels severely compromises the efficacy of the available therapies. In the past decade, increasing efforts have been made to understand the complexity of these tumours and to develop new diagnostic tools and therapies that might help to improve patient outcomes. In this expert Consensus Statement, which is endorsed by the European Network for the Study of Cholangiocarcinoma, we aim to summarize and critically discuss the latest advances in CCA, mostly focusing on classification, cells of origin, genetic and epigenetic abnormalities, molecular alterations, biomarker discovery and treatments. Furthermore, the horizon of CCA for the next decade from 2020 onwards is highlighted.

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Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study

Ghassan Abou-Alfa, Vaibhav Sahai, Antoine Hollebecque … (2020)

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.

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Author and article information

Contributors

A. Vogel

Journal

Journal ID (nlm-ta): ESMO Open

Journal ID (iso-abbrev): ESMO Open

Title: ESMO Open

Publisher: Elsevier

ISSN (Electronic): 2059-7029

Publication date PMC-release: 04 June 2024

Publication date Collection: June 2024

Publication date (Electronic): 04 June 2024

Volume: 9

Issue: 6

Electronic Location Identifier: 103488

Affiliations

[1 ]Hannover Medical School, Hannover, Germany

[2 ]Toronto General Hospital, Toronto

[3 ]Princess Margaret Cancer Centre, Toronto, Canada

[4 ]University of Michigan, Ann Arbor, USA

[5 ]Gustave Roussy Cancer Center, Paris, France

[6 ]Providence Cancer Center, Portland, USA

[7 ]Università degli studi di Verona, Verona, Italy

[8 ]University of Kansas Medical Center, Kansas City

[9 ]Baylor University Medical Center, Dallas

[10 ]Mayo Clinic Cancer Center, Phoenix

[11 ]Morristown Memorial Hospital, Morristown

[12 ]Johns Hopkins University School of Medicine, Baltimore, USA

[13 ]Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, Republic of Korea

[14 ]Fox Chase Cancer Center, Philadelphia

[15 ]University of Chicago Medicine, Chicago, USA

[16 ]University Hospitals Gasthuisberg, Leuven & University of Leuven, Leuven, Belgium

[17 ]Incyte Corporation, Wilmington, USA

[18 ]Incyte International Biosciences Sàrl, Morges, Switzerland

[19 ]Memorial Sloan Kettering Cancer Center, New York

[20 ]Weill Medical College at Cornell University, New York, USA

[21 ]Trinity College Dublin School of Medicine, Dublin, Ireland

Author notes

[∗ ] Correspondence to: Prof. Arndt Vogel, Toronto General Hospital, University Health Network, 200 Elizabeth Street, Toronto, ON, M5G 2C4, Canada. Tel: +49 176 1 532 9590 vogela@ 123456me.com

[☆]

Note: These data have been previously presented in part at the ESMO World Congress on Gastrointestinal Cancer (Barcelona, Spain; 29 June-2 July 2022), the ILCA 2022 Annual Conference (Madrid, Spain; 1-4 September 2022), and the BASL Annual Meeting (Leeds, UK; 20-23 September 2022).

Article

Publisher Item ID: S2059-7029(24)01257-2 Publisher ID: 103488

DOI: 10.1016/j.esmoop.2024.103488

PMC ID: 11190465

PubMed ID: 38838500

SO-VID: b0bf56bb-4ee0-47a1-92c9-dd8608a313a0

License:

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

An open-label study of pemigatinib in cholangiocarcinoma: final results from FIGHT-202☆

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Abstract

Background

Patients and methods

Results

Conclusions

Highlights

Related collections

DrugRxiv

Most cited references 39

Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer.

Cholangiocarcinoma 2020: the next horizon in mechanisms and management

Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study

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