Entrectinib Medicine 13 December 2018 Extended indication Rozlytrek as monotherapy is indicated for the treatment of adult and paediatric patients 12 years of age and older, with solid tumours expressing a neurotrophic tyrosine receptor kinase (NTRK) gene fusion, who have a disease that is locally advanced, metastatic or where surgical resection is likely to result in severe morbidity, and who have not received a prior NTRK inhibitor or who have no satisfactory treatment options. Therapeutic value Possible equal value Total cost € 3,445,000.00 Registration phase Registered Product Active substance Entrectinib Domain Oncology and Hematology Reason of inclusion New medicine (specialité) Main indication Oncology other Extended indication Rozlytrek as monotherapy is indicated for the treatment of adult and paediatric patients 12 years of age and older, with solid tumours expressing a neurotrophic tyrosine receptor kinase (NTRK) gene fusion, who have a disease that is locally advanced, metastatic or where surgical resection is likely to result in severe morbidity, and who have not received a prior NTRK inhibitor or who have no satisfactory treatment options. Current proprietary name Already available biosimilars / generics Proprietary name Rozlytrek Manufacturer Roche Portfolio holder Mechanism of action Tyrosine kinase inhibitor Route of administration Oral Therapeutical formulation Tablet Budgetting framework Intermural (MSZ) Centre of expertise Additional remarks Inhibitor of the tyrosine kinases TrkA (coded by the gene NTRK1), TrkB (coded by the gene NTRK2), TrkC (coded by the gene NTRK3), ROS1 (coded by the gene ROS1), and ALK (coded by the gene ALK). Registration Registration route Centralised (EMA) Type of trajectory Unknown Particularity Unknown ATMP Unknown Submission date January 2019 Expected Registration July 2020 Orphan drug No Registration phase Registered Reimbursement Medicine sluice Additional remarks Positieve CHMP-opinie mei 2020. Therapeutic value Current treatment options Afhankelijk van tumor type en in de toekomst larotrectinib. Therapeutic value Possible equal value This assessment does not indicate any potential inclusion in the package. Substantiation Er is geen directe vergelijking met larotrectinib maar de verwachting is dat deze twee geneesmiddelen gelijkwaardig zullen zijn. Duration of treatment Median 12.9 month / months Frequency of administration 1 times a day Dosage per administration 600 mg References SmPC. Additional remarks Expected patient volume per year Patient volume 30 - 76 Market share is generally not included unless otherwise stated. Maximum patient volume for sluice References NKR; Hartwig Medical Foundation, 2018; Stransky et al. Nat Commun. 2014 Sep 10; 5: 4846; Gatalica et al. Mod Pathol. 2019 Jan;32(1):147-153; Fabrikant Additional remarks De prevalentie van NTRK gen fusie is 0,3%. Van de 46.000 nieuw gediagnosticeerde patiënten met stadium III-IV kanker hebben circa 138 patiënten een NTRK gen fusie. Patiënten komen in aanmerking voor entrectinib na eerdere systemische therapie te hebben ontvangen (indien beschikbaar). Volgens de NKR heeft 55% van de stadium III-IV patiënten minimaal 1 lijn therapie ontvangen. Dit komt neer op 76 patiënten. Slechts patiënten met een aangetoonde NTRK gen fusie komen in aanmerking voor therapie. 2-3 jaar na introductie van de eerste EGFR, ROS of ALK inhibitors werd circa 40% van de patiënten die in aanmerking komen voor testen getest is op deze mutaties. Dit betekent een mogelijk realistisch patiëntvolume van 30 patiënten. De werkgroep geeft aan dat de inschatting van 30 patiënten erg onzeker is, de daadwerkelijke aantallen zullen nog onderzocht moeten worden in de praktijk. Entrectinib zal de concurrentie moeten aangaan met larotrectinib. Expected cost per patient per year Cost € 65,000.00 This amount gives an indication of the total cost. It is the result of the average expected patient volume times the average cost per patient. both per year. References Fabrikant. Additional remarks De fabrikant geeft aan dat de prijs €65.000 per patiënt per jaar zal bedragen. Potential total cost per year Total cost € 3,445,000.00 Total cost for sluice Additional remarks Off label use Off label use No Indications off label use References Fabrikant. Additional remarks Indication extension Indication extensions Yes Indication extensions Patiënten ROS1-positief geavanceerde of gemetastaseerde NSCLC (stadium IIIb/IV) References Fabrikant. Additional remarks Other information Additional remarks