Safety profile for PEMAZYRE — 1 of 1
The safety profile of PEMAZYRE was investigated in the FIGHT–202 study
In FIGHT-202, the most common AR observed with PEMAZYRE was hyperphosphataemia1
- The safety of PEMAZYRE was investigated in the FIGHT–202 study in previously treated patients with CCA (N=147)1
and additional information
Warnings and precautions
For further safety information, please refer to the PEMAZYRE Swissmedic Professional Information.1
Healthcare professionals are required to report any suspected new or serious side effects. See the “Undesirable effects” section of the Swissmedic Professional Information for the terms and conditions for reporting side effects. Adverse events should also be reported to Incyte immediately by phoning 00800 000 274 23 or via email at firstname.lastname@example.org.
MOST COMMON ARs OBSERVED WITH
Most common ARs (any grade)
- The most common serious ARs with PEMAZYRE were:1
- Hyponatraemia (2.0%)
- Blood creatinine increase (1.4%)
- No serious AR led to PEMAZYRE dose reduction1
- One serious AR of hyponatraemia (0.7%) led to dose interruption. One serious AR of blood creatinine increase (0.7%) led to dose discontinuation1
- Eye disorder serious ARs were retinal detachment (0.7%), non-arteritic optic ischaemic neuropathy (0.7%) and retinal artery occlusion (0.7%)1
Description of specific adverse reactions and additional information
- Hyperphosphataemia was reported in 60.5% of all patients treated with PEMAZYRE and usually developed within the first 15 days. None of the reactions were ≥ Grade 3 in severity, serious or led to discontinuation of PEMAZYRE1
- Dose interruption occurred in 1.4% of patients and dose reduction in 0.7% of patients1
- These results suggest that dietary phosphate restriction and/or administration of phosphate-lowering therapy along with the 1-week dose holiday were effective strategies for managing this on-target effect of PEMAZYRE1
- Hypophosphataemia reactions were Grade ≥3 in 12.3% of patients1
Serous retinal detachment
- Serous retinal detachment occurred in 4.8% of all patients treated with PEMAZYRE1
- Reactions were generally Grade 1 or 2 (3.4%) in severity; ≥ Grade 3 and serious reactions included retinal detachment in one patient (0.7%)1
- Two ARs of retinal detachment (0.7%) and detachment of retinal pigment epithelium (0.7%) led to dose interruption. None of the reactions led to dose reduction or discontinuation1
- An increase from baseline in mean creatinine levels of approximately 16 μmol/L occurred on Days 8 and 15 of the 1st cycle. These higher lever generally returned close to baseline by Cycle 2 Day 1. Above-normal creatinine values occurred in 13% of patients at baseline, increased to 33.6% on Day 15 of Cycle 1 and were observed in approximately 20% to 30% of participants on Day 1 of subsequent cycles1
- The reactions were Grade 1 or 2 with the exception of 2 patients (1.4%) with Grade 3 changes, and resolved without sequelae1
- However, normal creatinine values were observed after a one-week treatment suspension period1
Warnings and precautions
- Hyperphosphataemia is a pharmacodynamic effect expected with PEMAZYRE administration1
- Prolonged hyperphosphataemia can cause precipitation of calcium-phosphate crystals that can lead to hypocalcaemia, soft tissue mineralisation, secondary hyperparathyroidism, muscle cramps, seizure activity, QT interval prolongation, and arrhythmias. Soft tissue mineralisation, including cutaneous calcification and calcinosis, have been observed with PEMAZYRE treatment1
- Recommendations for management of hyperphosphataemia include dietary phosphate restriction, administration of phosphate-lowering therapy and dose modification when required1
- Phosphate-lowering therapy was used by 28.5% of patients during treatment with PEMAZYRE1
- Discontinuing phosphate-lowering therapy and diet should be considered during PEMAZYRE treatment breaks or if serum phosphate level falls below normal range1
- Severe hypophosphataemia may present with confusion, seizures, focal neurological findings, heart failure, respiratory failure, muscle weakness, rhabdomyolysis, and hemolytic anaemia1
For patients presenting with hyperphosphataemia or hypophosphataemia, additional close monitoring and follow-up is recommended regarding dysregulation of bone mineralisation1
Serous retinal detachment
- PEMAZYRE can cause serous retinal detachment reactions, which may present with symptoms such as blurred vision, visual floaters, or photopsia. This can moderately influence the ability to drive and use machines1
- Ophthalmological examination, including OCT should be performed prior to initiation of therapy and every 2 months for the first 6 months of treatment, every 3 months afterwards, and urgently at any time for visual symptoms. For serous retinal detachment reactions, the dose modification guidelines should be followed1
- During the conduct of the clinical study, there was no routine monitoring, including OCT, to detect asymptomatic serous retinal detachment; therefore, the incidence of asymptomatic serous retinal detachment with PEMAZYRE is unknown
- Careful consideration should be taken with patients that have clinically significant medical eye disorders, such as retinal disorders, including but not limited to, central serous retinopathy, macular/retinal degeneration, diabetic retinopathy, and previous retinal detachment1
- PEMAZYRE can cause dry eye. Patients should use ocular demulcents in order to prevent or treat dry eye as needed1
- Based on the mechanism of action and findings in an animal reproduction study, PEMAZYRE can cause foetal harm when administered to a pregnant woman. Pregnant women should be advised of the potential risk to the foetus1
- Women of childbearing potential should be advised not to become pregnant and men should be advised not to father a child during treatment1
- An effective method of contraception should be used during treatment with PEMAZYRE and for 1 week following completion of therapy1
- A pregnancy test should be performed before treatment initiation to exclude pregnancy1
Blood creatinine increase
- PEMAZYRE may increase serum creatinine by decreasing renal tubular secretion of creatinine; this may occur due to inhibition of renal transporters OCT2 and MATE1 and may not affect glomerular function1
- Within the first cycle, serum creatinine increased (mean increase of 0.2 mg/dL) and reached steady state by Day 8, and then decreased during the 7 days off therapy. Alternative markers of renal function should be considered if persistent elevations in serum creatinine are observed1
- 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 PEMAZYRE is expected to be low1
- PEMAZYRE® (pemigatinib) Swissmedic Professional Information, June 2021; https://www.swissmedicinfo.ch/ (accessed 02 December 2021).
- Rizvi S and Borad MJ. The rise of the FGFR inhibitor in advanced biliary cancer: the next cover of Time magazine? J Gastrointest Oncol. 2016;7:789–96.
- Ghouri YA, et al. Cancer review: Cholangiocarcinoma. J Carcinog. 2015;14:1.
- Sharma P and Yadav S. Demographics, tumor characteristics, treatment, and survival of patients with Klatskin tumors. Ann Gastroenterol. 2018;31:231–6.
- Blechacz B. Cholangiocarcinoma: Current knowledge and new developments. Gut Liver. 2017;11:13–26.
- Valle JW, et al. New horizons for precision medicine in biliary tract cancers. Cancer Discov. 2017;7:943–62.
- Bañales JM, et al. Cholangiocarcinoma 2020: The next horizon in mechanisms and management. Nat Rev Gastroenterol Hepatol. 2020;17:557–88.
- Bañales JM, et al. Expert consensus document: Cholangiocarcinoma: Current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA). Nat Rev Gastroenterol Hepatol. 2016;13:261–80.
- Bertuccio P, et al. A comparison of trends in mortality from primary liver cancer and intrahepatic cholangiocarcinoma in Europe. Ann Oncol. 2013;24:1667–74.
- Blechacz B, et al. Clinical diagnosis and staging of cholangiocarcinoma. Nat Rev Gastroenterol Hepatol. 2011;8:512–22.
- Forner A, et al. Clinical presentation, diagnosis and staging of cholangiocarcinoma. Liver Int. 2019;39(suppl 1):98–107.
- Valle JW, et al. Biliary cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016;27(suppl 5):v28–v37.
- Lamarca A, et al. Advanced intrahepatic cholangiocarcinoma: Post hoc analysis of the ABC-01, -02, and -03 clinical trials. J Natl Cancer Inst. 2020;112:200–10.
- Valle JW, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362:1273–81.
- Lamarca A, et al. Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): A phase 3, open-label, randomised, controlled trial. Lancet Oncol. 2021;22:690–701.
- Lowery MA, et al. Comprehensive molecular profiling of intrahepatic and extrahepatic cholangiocarcinomas: potential targets for intervention. Clin Cancer Res. 2018;24:4154–61.
- Jain A, et al. Cholangiocarcinoma with FGFR genetic aberrations: A unique clinical phenotype. JCO Precis Oncol. 2018;2:1–12.
- Ross JS, et al. New routes to targeted therapy of intrahepatic cholangiocarcinomas revealed by next-generation sequencing. Oncologist. 2014;19:235–42.
- Farshidfar F, et al. Integrative genomic analysis of cholangiocarcinoma identifies distinct IDH-mutant molecular profiles. Cell Rep. 2017;18:2780–94.
- Graham RP, et al. Fibroblast growth factor receptor 2 translocations in intrahepatic cholangiocarcinoma. Hum Pathol. 2014;45:1630–8.
- Churi CR, et al. Mutation profiling in cholangiocarcinoma: Prognostic and therapeutic implications. PLoS One. 2014;9:e115383.
- Arai Y, et al. Fibroblast growth factor receptor 2 tyrosine kinase fusions define a unique molecular subtype of cholangiocarcinoma. Hepatology. 2014;59:1427–34.
- Borad MJ, et al. Fibroblast growth factor receptor 2 fusions as a target for treating cholangiocarcinoma. Curr Opin Gastroenterol. 2015;31:264–68.
- Silverman IM, et al. Clinicogenomic analysis of FGFR2-rearranged cholangiocarcinoma identifies correlates of response and mechanisms of resistance to pemigatinib. Cancer Discov. 2021;11:326–39.
- Barr FG. Fusion genes in solid tumors: The possibilities and the pitfalls. Expert Rev Mol Diagn. 2016;16:921–3.
- Mosele F, et al. Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: A report from the ESMO Precision Medicine Working Group. Ann Oncol. 2020;31:1491–505.
- Liu PCC, et al. INCB054828 (pemigatinib), a potent and selective inhibitor of fibroblast growth factor receptors 1, 2, and 3, displays activity against genetically defined tumor models. PLoS One. 2020;15:e0231877.
- Abou-Alfa GK, et al. Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: A multicentre, open-label, phase 2 study. Lancet Oncol. 2020;21:671–84.
All references are available upon request
Abbreviated Prescribing Information
▼ This medicinal product is subject to additional monitorings. For further information, see product information Pemazyre on www.swissmedicinfo.ch.PEMAZYRE (pemigatinib), tablets of 13.5 mg, 9 mg, 4.5 mg. I: : As monotherapy for the treatment of adults with locally advanced, unresectable or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement that have progressed after at least one line of systemic therapy. P: Treatment should be initiated by a physician experienced in the diagnosis and treatment of patients with biliary tract cancer. FGFR2 fusion positivity status must be confirmed prior to initiation of therapy. Pemazyre 13.5 mg is taken orally once per day for 14 days, followed by 7 days off therapy. For dose adjustments due to adverse reactions, see www.swissmedicinfo.ch.For patients with severe hepatic or renal impairment, the dose should be reduced to the next lower strength. CI: : Hypersensitivity to the active substance or to any of the excipients. Concomitant use with St John’s wort. W/P: Pemazyre is associated with hyper- and hypophosphatemia, serous retinal detachment, dry eye and blood creatinine increase. Pemazyre can cause fetal harm. Women of childbearing potential should be advised not to become pregnant and men not to father a child during treatment. IA: Concomitant administration with proton pump inhibitors, strong CYP3A4 inhibitors or inducers should be avoided. Administration should be separated by at least 6 hours before or after administration of P-gp substrates with a narrow therapeutic index. Close clinical surveillance is recommended when co-administered with CYP2B6 substrates. UE: The most common adverse reactions (≥ 30%) were hyperphosphatemia, alopecia, diarrhea, nail toxicity, fatigue, nausea, dysgeusia, stomatitis, constipation and dry mouth. The most common serious adverse reactions were hyponatremia and increased blood creatinine. For further information on UE, see www.swissmedicinfo.ch. Dispensing cat.: A. Revision date: June 2021. Marketing authorisation holder: Incyte Biosciences International Sàrl, CH-1110 Morges. Refer to www.swissmedicinfo.ch for detailed information.
Resources and support
For further information, please refer to the PEMAZYRE Swissmedic Professional Information.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 email@example.com or contact us at our website: https://www.incyte.com/contact-us/medical-information.