Drugs Xagena
The European Medicines Agency (EMA) has recommended the conditional marketing authorization ( CMA ) of Futibatinib ( Lytgobi ) for the treatment of adult patients with locally advanced or metastatic cholangiocarcinoma ( CCA ) with a fibroblast growth factor receptor 2 ( FGFR2 )
fusion or rearrangement that have progressed after at least one prior line of systemic therapy.
Each year, approximately 6,000-8,000 individuals in Europe are diagnosed with cholangiocarcinoma, a rare cancer of the bile ducts of the liver, and approximately 0.3-6 people
per 100,000 individuals live with cholangiocarcinoma worldwide.
The positive opinion on Futibatinib is based on data from the pivotal phase 2 FOENIX-CCA2 trial in 103 patients with locally advanced or metastatic unresectable intrahepatic cholangiocarcinoma, harboring FGFR2 fusions or rearrangements who had received one or more prior lines of systemic therapy.
Patients in the trial received Futibatinib 20mg once daily until disease progression or unacceptable toxicity.
The trial’s primary endpoint was an objective response rate ( ORR ).
Results from the trial were published in the The New England Journal of Medicine ( NEJM ).
A total of 103 patients were enrolled in the FOENIX-CCA2 trial and received Futibatinib. A total of 43 of 103 patients (42% ) had a response, and the median duration of response was 9.7 months. Responses were consistent across patient subgroups, including patients with heavily pretreated disease, older adults, and patients who had co-occurring TP53 mutations.
At a median follow-up of 17.1 months, the median progression-free survival was 9.0 months and overall survival was 21.7 months.
Lytgobi may cause serious adverse reactions. The most common serious adverse reactions were intestinal obstruction and migraine.
The most common adverse reactions were hyperphosphatemia, nail disorders, constipation, alopecia, diarrhoea, dry mouth, fatigue, nausea, dry skin, increased AST, abdominal pain, stomatitis, vomiting, palmar-plantar erythrodysaesthesia syndrome, arthralgia, and decreased appetite.
Prolonged hyperphosphatemia may cause soft tissue mineralization, including cutaneous calcification, vascular calcification, and myocardial calcification, anaemia, hyperparathyroidism, and hypocalcemia that may cause muscle cramps, QT interval prolongation, and arrythmias. Hyperphosphatemia is a pharmacodynamic effect expected with Lytgobi administration. Recommendations for management of hyperphosphatemia include dietary phosphate restriction, administration of phosphate-lowering therapy, and dose modification when required.
Lytgobi can cause serous retinal detachment, which may present with symptoms such as blurred vision, visual floaters or photopsia. Ophthalmological examination should be performed prior to initiation of therapy, 6 weeks thereafter, and urgently at any time for visual symptoms. For serous retinal detachment reactions, the dose modification guidelines should be followed.
Lytgobi should not be used during pregnancy unless the clinical condition of the women requires treatment with Lytgobi.
Futibatinib is an oral, potent, selective, and irreversible tyrosine kinase inhibitor of FGFR1, 2, 3 and 4 being studied as a potential treatment for patients with advanced solid tumors with FGFR1-4 genetic aberrations, including cholangiocarcinoma, who were previously treated with chemotherapy or othertherapies.
Futibatinib covalently binds to the ATP binding pocket of FGFR1-4 resulting in the inhibition of FGFR-mediated signal transduction pathways, reduced tumor cell proliferation in tumors with FGFR1-4 genetic aberrations. ( Xagena )
Source: Taiho Oncology Europe, 2023
XagenaMedicine_2023
