Global Expanded Access Program for Pemigatinib in Patients with Previously Treated Locally Advanced or Metastatic Cholangiocarcinoma and Fibroblast Growth Factor Receptor Gene Alterations

Anouk Lindley; Gerald Prager; Michael Bitzer; Timothy C. Burn; Christine F. Lihou; Elisabeth Croft

doi:10.4143/crt.2023.1197

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Original Article Gastrointestinal cancer Global Expanded Access Program for Pemigatinib in Patients with Previously Treated Locally Advanced or Metastatic Cholangiocarcinoma and Fibroblast Growth Factor Receptor Gene Alterations: Anouk Lindley¹, Gerald Prager², Michael Bitzer³, Timothy C. Burn¹, Christine F. Lihou¹, Elisabeth Croft^1,; Cancer Research and Treatment : Official Journal of Korean Cancer Association 2024;56(3):847-855.
DOI: https://doi.org/10.4143/crt.2023.1197
Published online: February 7, 2024

¹Incyte Corporation, Wilmington, DE, USA

²Medical University of Vienna, Department of Internal Medicine I, Comprehensive Cancer Center Vienna, Vienna, Austria

³Department of Internal Medicine I, Eberhard-Karls University, Tübingen, Germany

Correspondence: Elisabeth Croft, Incyte Corporation, 1815 Augustine Cut Off, Wilmington, DE 19803, USA
Tel: 1-302-498-5285 E-mail: erichards@incyte.com

• Received: November 8, 2023 • Accepted: February 6, 2024

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Abstract

Purpose
Pemigatinib is a fibroblast growth factor receptor-2 (FGFR2) inhibitor approved for use in patients with previously treated cholangiocarcinoma (CCA) and FGFR2 fusions or rearrangements. This ongoing global Expanded Access Program (EAP) allows physicians in regions where pemigatinib is not commercially available to request pemigatinib for patients with locally advanced or metastatic CCA who, in the physician’s opinion, could benefit from pemigatinib treatment.
Materials and Methods
Eighty-nine patients from Europe, North America, and Israel were treated from January 2020 through September 2021.
Results
Patients had FGFR gene fusions (68.5%), rearrangements (12.4%), translocations (5.6%), amplifications (2.2%), and other alterations (11.2%). Median duration of treatment in the EAP was 4.0 months (range, 0.1 to 13.6 months). The most frequently reported adverse event (AE) was hyperphosphatemia (22.5%); the most common serious AE was cholangitis (3.4%). Treatment discontinuation was associated with reports of AEs for seven patients (7.9%). AEs associated with pemigatinib were consistent with those observed in clinical trials.
Conclusion
Efficacy was not assessed in this EAP. However, some patients remained on treatment for up to a year, suggesting that they observed a benefit from treatment. Patients with CCA should undergo molecular testing to identify those who could benefit from targeted treatments such as pemigatinib.
Key words: Pemigatinib, Cholangiocarcinoma, FGFR2 fusions, FGFR2 rearrangements, Expanded Access Program

Introduction

Cholangiocarcinoma (CCA), originating from cholangiocytes in the intrahepatic or extrahepatic (perihilar or distal) biliary tree [1], is the second most common hepatic cancer [2]. Fusions or rearrangements of the fibroblast growth factor receptor-2 (FGFR2) gene, reported to occur in 8.8%-16.7% of CCAs [3-5], can result in constitutive activation of the FGFR2 protein [3,5] and are known oncogenic drivers [3-5]. Among patients with CCA, these FGFR2 fusions occur almost exclusively in intrahepatic versus extrahepatic CCA (95.2%-100.0%) [3-5]. Alterations in other FGFR family genes, including FGFR1 and FGFR3, are also observed in CCA, but are less common [4]. The prognosis of CCA is poor, with an estimated 5-year mortality rate of 80%, based on Surveillance, Epidemiology, and End Results (SEER) data from patients diagnosed with CCA between 2001 and 2017 [6]. At diagnosis, most tumors are too far advanced for curative resection, and tumor recurrence rates after resection are high [7,8]. For the first-line treatment of patients with unresectable, advanced CCA, European Society of Medical Oncology (ESMO) guidelines recommend cisplatin plus gemcitabine as standard of care and recommend considering the addition of durvalumab to this combination [9,10].

Pemigatinib is a selective, potent, oral inhibitor of FGFR1, FGFR2, and FGFR3 [11]. The phase II study, FIGHT-202, was conducted in patients with previously treated locally advanced or metastatic CCA with and without FGFR2 fusions or rearrangements [12]. In the cohort of 108 patients with FGFR2 fusions or rearrangements, overall response rate was 37.0% (95% confidence interval [CI], 27.9% to 46.9%)—four complete and 36 partial responses were observed—and median progression-free survival was 7.0 months (95% CI, 6.1 to 10.5 months) [13]. Median overall survival was 17.5 months (95% CI, 14.4 to 22.9) [13]. This represents an improvement in overall survival outcomes compared with that reported for second-line chemotherapy in patients with intrahepatic CCA (median, 13.4 months) [14]. Based on the results of the FIGHT-202 study, pemigatinib is approved in multiple countries for the treatment of patients with previously treated, unresectable locally advanced or metastatic CCA with an FGFR2 fusion or other rearrangement. Here, we report initial findings from an ongoing global pemigatinib Expanded Access Program (EAP), which allows physicians in areas where pemigatinib has not yet been approved to request access to pemigatinib for individual patients who, in their opinion and clinical judgment, would benefit from pemigatinib treatment of locally advanced or metastatic CCA that could not be treated satisfactorily with an authorized medicinal product.

Materials and Methods

1. Program design

In this EAP, pemigatinib was supplied in response to unsolicited physician requests on a named patient basis. The web-based program platform MyAccess Programs (Parexel, Newton, MA) was used to manage treating physician registration, patient enrollment, and pemigatinib order and reorder. Treating physicians registered in MyAccess and submitted information concerning their patient to confirm the patient’s eligibility to receive pemigatinib. The sponsor then acknowledged the request and advised the physician on the admissibility of the patient. If the patient was approved, the physician was asked to sign a letter of agreement and to provide all necessary local regulatory and independent ethics committee or institutional review board approvals. Treating physicians could then request a supply of pemigatinib for their patient via MyAccess. Some patients were approved for treatment before the launch of the online portal, so their review and approval were not completed within the MyAccess system. To participate in the EAP, patients and/or their legal representatives were required to sign a written informed consent and/or assent.

2. Patients

Patients ≥ 18 years of age with locally advanced or metastatic CCA and documented FGFR2 fusion or rearrangement were eligible to participate per the program guidelines. Patients with other FGFR alterations were also enrolled if their physician and the sponsor agreed they could potentially benefit from pemigatinib treatment. Patients were required to have radiographically evaluable disease per Response Criteria in Solid Tumors (RECIST) ver. 1.1 and documented disease progression or intolerance after at least one line of prior systemic therapy. Patients also had to be willing to avoid pregnancy or fathering children during pemigatinib treatment.

Patients were excluded if they were eligible to participate in an ongoing clinical trial of pemigatinib. Other exclusion criteria included brain or central nervous system metastases that were untreated or had progressed; concurrent anticancer therapy; radiation therapy within 4 weeks; abnormal laboratory parameters; a history of calcium and phosphate hemostasis disorder or systemic mineral imbalance with ectopic calcification of soft tissues; a clinically significant corneal or retinal disorder; and a history of hypovitaminosis D.

3. Treatment

Patients were instructed to take pemigatinib orally at approximately the same time daily. Each treatment cycle consisted of 14 days of pemigatinib treatment, followed by 7 days without the drug. The starting dose of 13.5 mg daily was supported by pharmacokinetic and pharmacodynamic results from a phase I/II study of pemigatinib in patients with advanced malignancies [15]. Treatment was to continue for as long as clinical benefit was observed, until treatment withdrawal criteria were met per the judgment of the treating physician, and as long as pemigatinib was accessible in the patient’s country of residence, the EAP was terminated by the sponsor, or the EAP expired in accordance with the national regulatory approval timeline for product launch. Patients were to discontinue pemigatinib if they became pregnant or withdrew consent, if treatment would be injurious to their health or well-being, if unacceptable toxicity occurred, if disease progression was reported, or if another antineoplastic treatment was initiated. Pemigatinib treatment could be interrupted to allow for resolution of toxicity (S1 Table). Doses could be reduced from 13.5 mg to 9 mg, and from 9 mg to 4.5 mg. Dose reduction below 4.5 mg was not permitted.

Hyperphosphatemia is an expected on-target pharmacologic effect of FGFR inhibition. Patients were to initiate a low-phosphate diet if their serum phosphate exceeded 5.5 mg/dL. Physicians were to consider the addition of phosphate-lowering therapy if serum phosphate exceeded 7 mg/dL. Guidance for the interruption/discontinuation of pemigatinib with respect to hyperphosphatemia is shown in S2 Table. A comprehensive eye examination was to be performed by a qualified ophthalmologist before the first dose, once every three cycles, and as clinically indicated. Treating physicians were to follow standard-of-care procedures and activities. Visit intervals were defined by standard of care for CCA in each country.

4. Data collection and statistical analyses

There was no upper limit on the number of patients who could participate in the EAP. Data were collected for demographics, duration of therapy, dosing and discontinuations, FGFR2 testing and status, and safety. All data are reported descriptively.

Once patients signed the informed consent form, their treating physicians were responsible for documenting and reporting adverse events (AEs) and serious AEs (SAEs) until the patient ceased participation in the EAP. AEs that began or worsened after informed consent were to be recorded in MyAccess. New AEs were to be monitored for at least 28 days after the last dose of pemigatinib. The severity of AEs was assessed using Common Terminology Criteria for Adverse Events ver. 5.0 grades 1 to 4. Physicians recorded whether they believed the AE was related to pemigatinib, the action taken with regard to pemigatinib, the event outcome, and its seriousness. AEs were regarded as SAEs if they were fatal or life-threatening, required or prolonged hospitalization, resulted in persistent or significant disability, constituted a congenital abnormality or birth defect, or were considered to be an important medical event that did not fit the other criteria.

Results

1. Patients

A total of 107 patients treated by 66 physicians were approved for pemigatinib through the EAP from January 2020 through September 2021. Of these, 89 received pemigatinib during that time. Most patients resided in Europe (83.1%), including 31 (34.8%) from Germany; other patients were residents of Canada (11.2%), the United States (3.4%), and Israel (2.2%) (Fig. 1). Median patient age was 61 years (interquartile range [IQR], 48 to 67 years); 65.2% of patients were women (Table 1). Prior treatments were reported for most patients (78.7%). The most commonly reported first-line therapy was cisplatin plus gemcitabine (55.1%), followed by leucovorin calcium, fluorouracil, and irinotecan (FOLFIRI; 7.9%) (Table 1). Eighteen patients (20.2%) had multiple prior successive treatments reported (Table 1). Two patients received prior targeted therapies, including one treated with lenvatinib and another with ponatinib, lenvatinib, olaparib, and infigratinib. The latter patient received pemigatinib through the EAP for 0.9 months only.

Patients were most commonly tested for FGFR alterations using the FoundationOne (41.6%), ThermoFisher Oncomine (18.0%), and Illumina (14.6%) platforms (Table 1, Fig. 1). Most patients had an alteration in FGFR2 (92.1%); four (4.5%) had an alteration in FGFR3, two (2.2%) had an alteration in FGFR1, and one (1.1%) had an unspecified FGFR alteration (Table 1). The most common alteration type was gene fusion (68.5%), followed by rearrangement (12.4%), other alteration (11.2%), translocation (5.6%), and amplification (2.2%) (Table 1). Further information on gene alterations is given in S3 Table.

2. Treatment

Median duration of treatment was 4.0 months (IQR, 1.8 to 7.1; range, 0.1 to 13.6 months) (Fig. 2); 27 patients (30%) were on treatment for more than 6 months. A total of 63 patients (70.8%) had discontinued pemigatinib as of the data cutoff date, leaving 26 (29.2%) still on treatment. Reasons for treatment discontinuation were not reported for most patients. Seven patients (7.9%) discontinued pemigatinib treatment on the same date that AEs were reported for them. Twenty-nine patients (32.6%) were reported to have discontinued the EAP due to the program being terminated in their country and eligible patients being transitioned to commercially available pemigatinib.

No patterns were observed in durations of treatment as a function of FGFR alteration type (Fig. 2). Alterations observed in the top decile of treatment duration (duration of 10.1 to 13.6 months) were FGFR2 fusions (six patients), an FGFR2 exon 1-17 rearrangement, an FGFR1 fusion, and an FGFR2 translocation. Alterations observed in the lowest decile for treatment duration (duration of 2 to 18 days) were FGFR2 translocation, an FGFR2 intron 17 rearrangement, FGFR2 fusions (four patients; one patient had two different FGFR2 fusions), an FGFR2 amplification, an unspecified alteration in FGFR2, and an FGFR3 fusion. Duration of treatment for patients with alterations in FGFR1 or FGFR3 ranged from 0.6 months to 12.1 months. Two patients had FGFR1 fusions, one of whom received treatment for 5.5 months, and other was on treatment for 12.1 months in the EAP before transitioning to commercial supply. The three patients with FGFR3 fusions had treatment durations of 0.6, 2.5, and 3.2 months; the patient with an unspecified FGFR3 alteration was on treatment for 3.3 months.

Among the 52 patients who appeared to receive pemigatinib as second-line treatment (patients with exactly one prior treatment reported), median treatment duration was 4.2 months (IQR, 2.5 to 7.0 months). Fourteen of these patients (24.6%) were still continuing in the EAP at the data cutoff date.

All patients had a starting dose of pemigatinib of 13.5 mg once daily; 17 (19.1%) had their dose reduced to 9 mg once daily. For three of these patients (3.4%), the dose was further reduced to 4.5 mg once daily. The median time to first dose reduction was 1.6 months (IQR, 1.1 to 3.1 months).

3. Safety

Of the 89 patients, 54 (60.7%) reported 161 AEs and SAEs. Seventeen patients (19.1%) reported at least one SAE. The most common nonserious AEs were hyperphosphatemia (22.5%), aspartate aminotransferase (AST) increased (10.1%), mucositis (9.0%), alanine aminotransferase (ALT) increased (7.9%), creatinine increased (7.9%), stomatitis (6.7%), diarrhea (5.6%), and dry mouth (5.6%) (Table 2). The most common SAEs were cholangitis (3.4%) and bleeding, death, disease progression, hypercalcemia, and kidney failure (all 2.2%) (Table 2).

Seven patients (7.9%) had AEs or SAEs reported on the same day as their discontinuation in the EAP. Eleven AEs and SAEs coinciding with pemigatinib discontinuation were reported for these patients. One patient was reported to have increased ALT, increased AST, and hyperbilirubinemia. One was reported to have creatinine increased, dry mouth, and parathyroid hormone increased. One patient each was reported to have bleeding (SAE), pleural effusion (SAE), and pulmonary embolism (SAE) on the date of treatment discontinuation. Disease progression coincided with treatment discontinuation in two patients, listed as an AE for one and an SAE for the other.

Discussion

This manuscript reports to results of an ongoing pemigatinib EAP for the treatment of patients with locally advanced or metastatic CCA and FGFR alterations. Among previously treated patients with CCA enrolled in the pemigatinib EAP, median duration of treatment was 4.0 months, with a range of 0.1 to 13.6 months, suggesting that some patients and their physicians perceive a benefit from pemigatinib treatment in a real-world setting.

Reported incidence of all-cause, any-grade AEs was lower in the EAP than in the FIGHT-202 pemigatinib clinical trial (60.7% vs. 100%); the rate of SAEs was also lower in these patients than in FIGHT-202 (19.1% vs. 45.0%) [12]. However, this difference may be an effect of how these AE data were collected. In the FIGHT-202 clinical trial, AE data were actively solicited and collected. In the EAP, AEs were not solicited; reporting of AEs was the responsibility of the treating physician. As in FIGHT-101, FIGHT-202, and another study of pemigatinib [12,15,16], the most common AE was hyperphosphatemia. In addition, the overall profile of AEs observed in the EAP differed from that reported for FIGHT-202. For example, the incidence of hyperphosphatemia (22.5%) reported in the EAP was lower than that observed in FIGHT-202 (60%).

Alopecia was reported in 49% of patients in FIGHT-202, with diarrhea (47%), fatigue (42%), and dysgeusia (40%) also being commonly reported [12]. In the EAP, these events were reported in 3.4%, 5.6%, 3.4%, and 0% of patients, respectively. Nail toxicities were reported for 42% of patients in FIGHT-202 [12], but only 4.5% of patients (n=4) in the EAP. In contrast, increased AST and increased ALT were the second and third most commonly reported events overall in the EAP (reported in 11.2% and 9.0% of patients respectively), but were each reported in 7% of patients in FIGHT-202 [12]. This observation may reflect the fact that patients in the EAP were not selected on the basis of hepatic function, whereas patients in FIGHT-202 were required to have adequate hepatic function. Patients in the EAP may also have been less fit or had more advanced disease or more comorbidities than patients in FIGHT-202 who were required to have adequate physical performance (Eastern Cooperative Oncology Group [ECOG] performance status of 0-2). Many of the AEs reported in the EAP were expected on-target toxicities given the mechanism of action of pemigatinib as an FGFR inhibitor, including hyperphosphatemia, skin toxicities (e.g., mucositis, stomatitis), and ocular toxicities (e.g., retinal pigment epithelial detachment) [17].

The percentage of patients in the EAP who had an AE reported at the same time as treatment discontinuation (7.9%) was similar to the percentage of patients in FIGHT-202 who discontinued treatment due to AEs (9%) [12]. Data for patients discontinuing treatment due to AEs may be more accurately reflected than other AEs in the EAP, as physicians would have reported these AEs at the same time they discontinued their patients from the program.

The median duration of treatment observed here (4.0 months) is shorter than that observed in FIGHT-202 (7.2 months) for 107 patients with FGFR2 fusions or rearrangements [12]. However, the differences in patient populations make it difficult to compare these data. In addition, about a third of patients were reported to be discontinuing the EAP due to the program being terminated in their country and eligible patients being transitioned to commercially available pemigatinib. This suggests that the treatment duration within the EAP of 4.0 months may be an underestimation of the real treatment duration. We have no data on how long these patients continued pemigatinib once they left the EAP.

A small subset of the patient population in this EAP had alterations in FGFR1 and FGFR3. Both patients with FGFR1 fusions had durations of treatment longer than the median (5.5 and 12.1 vs. 4.0 months), and one transitioned to commercial pemigatinib. All patients with FGFR3 alterations had treatment durations shorter than the median (0.6-3.3 vs. 4.0 months). Given the small number of enrolled patients with FGFR1 or FGFR3 alterations, whether pemigatinib treatment can provide robust benefit in patients with these alterations requires further investigation.

Limitations of this EAP include a lack of central testing— various platforms for testing FGFR genetic alterations were used, and results were reported inconsistently by different treating physicians. Because of this, it was not possible to delineate clinical features that are associated with FGFR alterations in patients enrolled in this EAP. However, for patients enrolled in FIGHT-202 with FGFR2 fusions/rearrangements versus no FGF/FGFR alterations, it was found that a greater percentage were women (61% vs. 44%), more had intrahepatic CCA (98% vs. 61%), more were aged < 65 years (77% vs. 39%), and fewer had ECOG performance status of 2 (5% vs. 17%) [12]. A further limitation of the study was that response data were not collected—this was beyond the scope of the EAP, which was intended to allow access to pemigatinib without significant restriction by the program sponsor.

In conclusion, these real-world data indicate that AEs associated with pemigatinib in routine use are similar to those observed in clinical trials, with hyperphosphatemia being the most common. A substantial percentage of patients remained on pemigatinib treatment for multiple treatment cycles, with 30% remaining on treatment for more than 6 months. Patients with CCA should undergo molecular testing to identify actionable genomic alterations. Pemigatinib treatment should be considered for those patients with genomic alterations in FGFR2. Future prospective randomized controlled studies are required to confirm the benefit of pemigatinib in patients with FGFR2 altered CCA. In this regard, a phase III randomized clinical trial (FIGHT-302) is currently recruiting patients in Europe, North America, and Asia to assess pemigatinib as a first-line treatment in comparison with cisplatin plus gemcitabine chemotherapy in patients with unresectable or metastatic CCA and an FGFR2 rearrangement (NCT03656536).

Electronic Supplementary Material

Supplementary materials are available at Cancer Research and Treatment website (https://www.e-crt.org).

crt-2023-1197-S1-Table.pdf

crt-2023-1197-S2-Table.pdf

crt-2023-1197-S3-Table.pdf

NOTES

Ethical Statement

Patients and/or their legal representatives provided written informed consent and/or assent before participation.

Author Contributions

Conceived and designed the analysis: Lindley A, Burn TC, Croft E, Prager G, Bitzer M.

Collected the data: Prager G, Bitzer M.

Contributed data or analysis tools: Lindley A, Prager G, Bitzer M.

Performed the analysis: Burn TC, Lindley A.

Wrote the paper: Prager G, Bitzer M, Lihou CF, Croft E, Lindley A, Burn TC.

Methodology, validation, data curation, review & editing, project administration: Lindley A, Prager G, Bitzer M, Burn TC, Lihou CF, Croft E.

Conflicts of Interest

GP has received speaker honoraria from Amgen, Bayer, Bristol Myers Squibb, Celgene, Eli Lilly & Company, Halozyme, Merck Serono, Pierre Fabre, Roche, Sanofi, Servier, Shire, Taiho Pharmaceutical Group, and Terumo. MB has been involved as a consultant and expert witness in Incyte Biosciences Germany, Bayer Vital GmbH, EISAI GmbH, MSD Sharp & Dohme GmbH, Roche Pharma AG, and Taiho Oncology Europe GmbH. ECR owns stocks in Incyte Corporation. This program was sponsored by Incyte Corporation (Wilmington, DE). Medical writing assistance was provided by Peijia (Jessica) Yuan, PhD, of Envision Pharma Group (Fairfield, CT), and funded by Incyte Corporation. Assistance with data analysis was provided by Jennie G. Jacobson, PhD, of Incyte Corporation.

Acknowledgements

The authors wish to thank the patients, treating physicians, and associated healthcare professionals who participated in this program. The EAP program and the costs associated with this manuscript were funded by Incyte Corporation. The sponsor participated in collection of the data. Data were analyzed and interpreted by the authors, four of whom are current or former employees of the sponsor. An additional employee of the sponsor provided help with data analysis under the direction of the authors. Medical writing assistance was funded by the sponsor. All authors revised the intellectual content of the manuscript. Other employees of the sponsor reviewed the manuscript and provided comments. Final decisions on contents were made by the authors. The decision to submit the article was made by the authors and the authors approved the final manuscript.

Fig. 1.

Distribution of patients and FGFR2 tests in Europe (A), North America (B), and Israel (C). ^a)One patient had parallel testing with Illumina and Archer, ^b)One patient had parallel testing with Illumina and ThermoFisher Oncomine; therefore, percentages add up to > 100%.

Fig. 2.

Duration of therapy. Gray arrow indicates the patient was still on treatment at data cutoff (September 30, 2021). ^*Indicates that the patient was reported to be discontinuing the Expanded Access Program due to the program being discontinued or being transitioned to commercially available pemigatinib. Patients for whom the specific type of FGFR2 or FGFR3 alteration was unreported were categorized generally as ‘FGFR2 alteration’ or ‘FGFR3 alteration.’

Table 1.

Patient baseline demographics and clinical characteristics

Characteristic	No. (%) (n=89)
Age (yr), median (IQR)	61 (48-67)
Sex
Women	58 (65.2)
First-line treatment
Cisplatin+gemcitabine	49 (55.1)
Unspecified	19 (21.3)
FOLFIRI	7 (7.9)
GEMOX	5 (5.6)
Capecitabine	2 (2.2)
Carboplatin+paclitaxel	2 (2.2)
Other	5 (5.6)
No. of prior treatments
1	52 (58.4)
2	10 (11.2)
3	2 (2.2)
4	2 (2.2)
5	3 (3.4)
6	0
7	1 (1.1)
Unspecified	19 (21.3)
Testing^a)
Foundation Medicine	37 (41.6)
ThermoFisher Oncomine	16 (18.0)
Illumina (local assay)	13 (14.6)
Other	25 (28.1)
FGFR alteration
FGFR2	82 (92.1)
FGFR3	4 (4.5)
FGFR1	2 (2.2)
Unspecified FGFR alteration	1 (1.1)
FGFR alteration type
Fusion	61 (68.5)
Rearrangement	11 (12.4)
Other alteration	10 (11.2)
Translocation	5 (5.6)
Amplification	2 (2.2)

FGFR, fibroblast growth factor receptor; FOLFIRI, leucovorin calcium, fluorouracil, and irinotecan; GEMOX, gemcitabine, oxaliplatin; IQR, interquartile range.

^a) One patient had parallel testing with Illumina and Archer, and one patient had parallel testing with Illumina and ThermoFisher Oncomine; therefore, percentages add up to > 100%.

Table 2.

Adverse events or serious adverse events occurring in ≥ 2 patients

	No. (%) (n=89)
Adverse events
Hyperphosphatemia	20 (22.5)
AST increased	9 (10.1)
Mucositis	8 (9.0)
ALT increased	7 (7.9)
Creatinine increased	7 (7.9)
Stomatitis	6 (6.7)
Diarrhea	5 (5.6)
Dry mouth	5 (5.6)
Hypophosphatemia	4 (4.5)
Alopecia	3 (3.4)
Calcium increased	3 (3.4)
Fatigue	3 (3.4)
Abdominal pain	2 (2.2)
Anemia	2 (2.2)
Bleeding	2 (2.2)
Kidney injury	2 (2.2)
Nausea	2 (2.2)
Phosphate increased	2 (2.2)
Platelets decreased	2 (2.2)
Response evaluation	2 (2.2)
Retinal pigment epithelial detachment	2 (2.2)
Urinary tract infection	2 (2.2)
Serious adverse events
Cholangitis	3 (3.4)
Bleeding	2 (2.2)
Death	2 (2.2)
Disease progression	2 (2.2)
Hypercalcemia	2 (2.2)
Kidney failure	2 (2.2)

ALT, alanine aminotransferase; AST, aspartate aminotransferase.

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Precision oncology targeting FGFRs: A systematic review on pre-clinical activity and clinical outcomes of pemigatinib
Ludovica Gnagni, Ilary Ruscito, Ilaria Grazia Zizzari, Marianna Nuti, Chiara Napoletano, Aurelia Rughetti
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Global Expanded Access Program for Pemigatinib in Patients with Previously Treated Locally Advanced or Metastatic Cholangiocarcinoma and Fibroblast Growth Factor Receptor Gene Alterations

Cancer Res Treat. 2024;56(3):847-855. Published online February 7, 2024

DOI: https://doi.org/10.4143/crt.2023.1197

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Abstract
Introduction
Materials and Methods
Results
Discussion
Electronic Supplementary Material
NOTES
REFERENCES

Global Expanded Access Program for Pemigatinib in Patients with Previously Treated Locally Advanced or Metastatic Cholangiocarcinoma and Fibroblast Growth Factor Receptor Gene Alterations

Fig. 1. Distribution of patients and FGFR2 tests in Europe (A), North America (B), and Israel (C). a)One patient had parallel testing with Illumina and Archer, b)One patient had parallel testing with Illumina and ThermoFisher Oncomine; therefore, percentages add up to > 100%.

Fig. 2. Duration of therapy. Gray arrow indicates the patient was still on treatment at data cutoff (September 30, 2021). *Indicates that the patient was reported to be discontinuing the Expanded Access Program due to the program being discontinued or being transitioned to commercially available pemigatinib. Patients for whom the specific type of FGFR2 or FGFR3 alteration was unreported were categorized generally as ‘FGFR2 alteration’ or ‘FGFR3 alteration.’

Fig. 1.

Fig. 2.

Global Expanded Access Program for Pemigatinib in Patients with Previously Treated Locally Advanced or Metastatic Cholangiocarcinoma and Fibroblast Growth Factor Receptor Gene Alterations

Characteristic	No. (%) (n=89)
Age (yr), median (IQR)	61 (48-67)
Sex
Women	58 (65.2)
First-line treatment
Cisplatin+gemcitabine	49 (55.1)
Unspecified	19 (21.3)
FOLFIRI	7 (7.9)
GEMOX	5 (5.6)
Capecitabine	2 (2.2)
Carboplatin+paclitaxel	2 (2.2)
Other	5 (5.6)
No. of prior treatments
1	52 (58.4)
2	10 (11.2)
3	2 (2.2)
4	2 (2.2)
5	3 (3.4)
6	0
7	1 (1.1)
Unspecified	19 (21.3)
Testing^a)
Foundation Medicine	37 (41.6)
ThermoFisher Oncomine	16 (18.0)
Illumina (local assay)	13 (14.6)
Other	25 (28.1)
FGFR alteration
FGFR2	82 (92.1)
FGFR3	4 (4.5)
FGFR1	2 (2.2)
Unspecified FGFR alteration	1 (1.1)
FGFR alteration type
Fusion	61 (68.5)
Rearrangement	11 (12.4)
Other alteration	10 (11.2)
Translocation	5 (5.6)
Amplification	2 (2.2)

	No. (%) (n=89)
Adverse events
Hyperphosphatemia	20 (22.5)
AST increased	9 (10.1)
Mucositis	8 (9.0)
ALT increased	7 (7.9)
Creatinine increased	7 (7.9)
Stomatitis	6 (6.7)
Diarrhea	5 (5.6)
Dry mouth	5 (5.6)
Hypophosphatemia	4 (4.5)
Alopecia	3 (3.4)
Calcium increased	3 (3.4)
Fatigue	3 (3.4)
Abdominal pain	2 (2.2)
Anemia	2 (2.2)
Bleeding	2 (2.2)
Kidney injury	2 (2.2)
Nausea	2 (2.2)
Phosphate increased	2 (2.2)
Platelets decreased	2 (2.2)
Response evaluation	2 (2.2)
Retinal pigment epithelial detachment	2 (2.2)
Urinary tract infection	2 (2.2)
Serious adverse events
Cholangitis	3 (3.4)
Bleeding	2 (2.2)
Death	2 (2.2)
Disease progression	2 (2.2)
Hypercalcemia	2 (2.2)
Kidney failure	2 (2.2)

Table 1. Patient baseline demographics and clinical characteristics

FGFR, fibroblast growth factor receptor; FOLFIRI, leucovorin calcium, fluorouracil, and irinotecan; GEMOX, gemcitabine, oxaliplatin; IQR, interquartile range.

One patient had parallel testing with Illumina and Archer, and one patient had parallel testing with Illumina and ThermoFisher Oncomine; therefore, percentages add up to > 100%.

Table 2. Adverse events or serious adverse events occurring in ≥ 2 patients

ALT, alanine aminotransferase; AST, aspartate aminotransferase.