ESMO recommends routine use of multigene NGS to detect level 1 genomic alterations (IDH1 mutations, FGFR2 fusions, NTRK fusions and MSI-H) in advanced CCA27
Molecular profiling for early patient identification — 2 of 2
Testing for FGFR2 fusions or rearrangements can inform treatment decisions in CCA
The high frequency of actionable alterations in patients with CCA strongly supports the use of molecular testing in this population18
Scroll for more
References
- PEMAZYRE® (pemigatinib). Summary of Product Characteristics. (data cutoff: 08 July 2021).
- Rizvi S, et al. J Gastrointest Oncol. 2016;7:789–96.
- Ghouri YA, et al. J Carcinog. 2015;14:1.
- Sharma P, et al. Ann Gastroenterol. 2018;31:231–6.
- Blechacz B. Gut Liver. 2017;11:13–26.
- Valle JW, et al. Cancer Discov. 2017;7:943–62.
- Bañales JM, et al. Nat Rev Gastroenterol Hepatol. 2020;17:557–88.
- Bañales JM, et al. Nat Rev Gastroenterol Hepatol. 2016;13:261–80.
- Bertuccio P, et al. Ann Oncol. 2013;24:1667–74.
- Blechacz B, et al. Nat Rev Gastroenterol Hepatol. 2011;8:512–22.
- Forner A, et al. Liver Int. 2019;39:98–107.
- Vogel A, et al. Ann Oncol. 2023;34:127–40.
- Oneda E, Abu Hilal M and Zaniboni A. Cancers (Basel). 2020;12(5).
- NICE, 2021. Technology appraisal guidance [TA722]. Available at: https://www.nice.org.uk/guidance/ta722 (Accessed: November 2023).
- Scottish Medicines Consortium. Medicine: pemigatinib (brand name: Pemazyre®). Available at: https://www.scottishmedicines.org.uk/media/6653/de-pemigatinib-pemazyre-smc2399.pdf (Accessed: November 2023).
- NHS Wales HealthCollaborative. FGFR2 Gene Fusion Testing Clinical Guidance Document. Available from: https://executive.nhs.wales/networks/wales-cancer-network/wcn-documents/genomics/fgfr2-gene-fusion-testing-clinical-guideline/ (Accessed: November 2023).
- Lowery MA, et al. Clin Cancer Res. 2018;24:4154–61.
- Jain A, et al. JCO Precis Oncol. 2018;2:1–12.
- Ross JS, et al. Oncologist. 2014;19:235–42.
- Farshidfar F, et al. Cell Rep. 2017;18:2780–94.
- Graham RP, et al. Hum Pathol. 2014;45:1630–8.
- Churi CR, et al. PLoS One. 2014;9:e115383.
- Arai Y, et al. Hepatology. 2014;59:1427–34.
- Borad MJ, et al. Curr Opin Gastroenterol. 2015;31:264–8.
- Silverman I, et al. Cancer Discov. 2021;11:326–39.
- Barr FG, et al. Expert Rev Mol Diagn. 2016;16:921–3.
- Mosele F, et al. Ann Oncol. 2020;31:1491–505.
- Incyte Data on File (data cutoff: 08 July 2021).
- Abou-Alfa GK, et al. Lancet Oncol. 2020;21:671–84 (data cutoff: 22 March 2019).
Abbreviations
1L
first-line
2L
second-line
5-FU
5-fluorouracil
ASC
active symptom control
BRAF
v-raf murine sarcoma viral oncogene homolog B1
BTC
biliary tract cancer
CCA
cholangiocarcinoma
CI
confidence interval
CNS
central nervous system
CR
complete response
CYP2B6
cytochrome P450 2B6
CYP3A4
cytochrome P450 3A4
dCCA
distal cholangiocarcinoma
dMMR
mismatch repair deficient
DOR
duration of response
eCCA
extrahepatic cholangiocarcinoma
ECOG
Eastern Cooperative Oncology Group
EGFR
epidermal growth factor receptor
ESMO
European Society for Medical Oncology
EU
European Union
FGFR
fibroblast growth factor receptor
FOLFOX
folinic acid, fluorouracil and oxaliplatin
HER/neu
Human epidermal growth factor receptor
HR
hazard ratio
iCCA
intrahepatic cholangiocarcinoma
IDH
isocitrate dehydrogenase
KM
Kaplan-Meier
KRAS
Kirsten rat sarcoma viral oncogene homolog
MATE1
multidrug and toxin extrusion protein 1
MDT
multidisciplinary team
mg
milligram
mg/dL
milligram per decilitre
MHRA
Medicines and Healthcare products Regulatory Agency
MSI-H
microsatellite instability-high
NGS
next-generation sequencing
NTRK
neurotrophic tyrosine receptor kinase
OCT
optical coherence tomography
OCT2
organic cation transporter-2
ORR
overall response rate
OS
overall survival
pCCA
perihilar cholangiocarcinoma
P-gp
P-glycoprotein
PI
prescribing information
PPES
palmar-plantar erythrodysaesthesia syndrome
PR
partial response
PS
performance status
RECIST
Response Evaluation Criteria in Solid Tumours
SmPC
Summary of Product Characteristics
SOC
standard of care
Prescribing Information
PEMAZYRE®▼(pemigatinib) 4.5, 9, 13.5 mg tablets
contains Microcrystalline cellulose (E-460), Sodium starch glycolate (Type A), Magnesium stearate (E-572).
▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See below for how to report adverse reactions.
Indication: Pemazyre monotherapy is indicated for the treatment of adults with locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement that have progressed after at least one prior line of systemic therapy.
Dosage and administration: The recommended dose is 13.5 mg pemigatinib taken once daily for 14 days followed by 7 days off therapy. Therapy should be initiated by a physician experienced in biliary tract cancer. Confirm FGFR2 positive status prior to starting treatment. Treatment should be continued as long as the patient does not show evidence of disease progression or unacceptable toxicity.
Contraindications: Hypersensitivity to pemigatinib or excipients. Concomitant use of pemigatinib with St John’s wort.
Warnings and precautions: Consult the Summary of Product Characteristics (SmPC) for full details of potential toxicities and drug interactions, as well as information on monitoring and management, including recommended dose modifications.
Hyperphosphataemia: Hyperphosphataemia is a pharmacodynamic effect expected with pemigatinib. Effective management strategies for hyperphosphataemia include dietary phosphate restriction, phosphate-lowering therapy and dose modification. Consult the SmPC for full details.
Hypophosphataemia: Consider discontinuing phosphate-lowering therapy and increasing dietary phosphate if hypophosphataemia occurs. Consult the SmPC for full details.
Serous retinal detachment: Pemigatinib can cause serous retinal detachment reactions. Symptoms can include blurred vision, visual floaters, or photopsia. Ophthalmological examination, including optical coherence tomography (OCT) should be performed prior to starting pemigatinib and throughout treatment. Consult the SmPC for full details of OCT requirements and dose modification guidelines for serous retinal detachment reactions.
Dry eye: Pemigatinib can cause dry eye. Treat with ocular demulcents as needed.
Blood creatinine increase: Pemigatinib may increase serum creatinine by decreasing renal tubular secretion of creatinine. Alternative markers of renal function should be considered if persistent elevations in serum creatinine are observed.
Hepatic or renal impairment: Dose adjustment is recommended when administering pemigatinib to patients with severe hepatic or renal impairment.
Central nervous system (CNS) metastasis: Since untreated or progressing brain/CNS metastasis were not allowed in the study, efficacy in this population has not been evaluated and no dose recommendations can be made, however the blood-brain barrier penetration of pemigatinib is expected to be low.
Driving and operating machinery: Adverse reactions of fatigue and symptoms associated with retinal detachment may influence the ability to drive and operate machinery.
Drug interactions: If concurrent use of strong CYP3A4 inhibitors is necessary, the daily dose of pemigatinib should be reduced. Consult the SmPC for full details and for information on all potential drug interactions.
Pregnancy and breast-feeding: Pemigatinib can cause foetal harm when administered during pregnancy. Women of childbearing potential, including partners of male patients, should use effective contraception during treatment with pemigatinib and for 1 week after the last dose. Discontinue breast-feeding during treatment with pemigatinib and for 1 week following last dose.
Undesirable effects: The most common adverse drug reactions (ADRs) were hyperphosphataemia, alopecia, diarrhoea, nail toxicity, fatigue, nausea, dysgeusia, stomatitis, constipation, dry mouth, dry eye, arthralgia, hypophosphataemia, dry skin, and palmar-plantar erythrodysaesthesia syndrome. The most common serious adverse reactions were hyponatraemia and blood creatinine increase (see SmPC for details of all ADRs).
Quantities and marketing authorisation numbers:
4.5 mg dose (14 or 28 tablets) EU/1/21/1535/001-002, PLGB 42338/0008
9 mg dose (14 or 28 tablets) EU/1/21/1535/003-004, PLGB 42338/0009
13.5 mg dose (14 or 28 tablets) EU/1/21/1535/005-006, PLGB 42338/0010
Cost (ex. VAT): 4.5 mg x 14 tablets £7,159; 9 mg x 14 tablets £7,159; 13.5 mg x 14 tablets £7,159.
Legal categorisation: POM (prescription only medicine).
Marketing authorisation holder:
Great Britain: Incyte Biosciences UK Ltd, First Floor Q1, The Square, Randalls Way, Leatherhead, KT22 7TW, UK. UK (Northern Ireland): Incyte Biosciences Distribution B.V. Paasheuvelweg 25, 1105 BP Amsterdam, Netherlands.
Date of preparation: April 2021. UK/PEMA/P/21/0005
4.5 mg dose (14 or 28 tablets) EU/1/21/1535/001-002, PLGB 42338/0008
9 mg dose (14 or 28 tablets) EU/1/21/1535/003-004, PLGB 42338/0009
13.5 mg dose (14 or 28 tablets) EU/1/21/1535/005-006, PLGB 42338/0010
Cost (ex. VAT): 4.5 mg x 14 tablets £7,159; 9 mg x 14 tablets £7,159; 13.5 mg x 14 tablets £7,159.
Legal categorisation: POM (prescription only medicine).
Marketing authorisation holder:
Great Britain: Incyte Biosciences UK Ltd, First Floor Q1, The Square, Randalls Way, Leatherhead, KT22 7TW, UK. UK (Northern Ireland): Incyte Biosciences Distribution B.V. Paasheuvelweg 25, 1105 BP Amsterdam, Netherlands.
Date of preparation: April 2021. UK/PEMA/P/21/0005
Adverse events should be reported.
Reporting forms and information can be found at: www.mhra.gov.uk/yellowcard
or search for MHRA Yellow Card in the Google Play or Apple App Store.
Adverse events should also be reported to Incyte by calling 03301003677 (Great Britain)
00-800-0002-7423 (United Kingdom [Northern Ireland]).
Resources and support
For further information, please refer to the PEMAZYRE Summary of Product Characteristics (Great Britain and Northern Ireland).1
To request a meeting either for Incyte to contact you or to schedule a visit from an Incyte representative please click here.
To request further medical information, email us at eumedinfo@incyte.com or contact us at our website: https://www.incyte.com/contact-us/medical-information.