Nivolumab Medicine 13 December 2018 Extended indication Extension of Indication to include first-line treatment of adult patients with metastatic Non-Small Cell Lung Carcinoma (NSCLC) in combination with ipilimumab. Therapeutic value No judgement Total cost € 56,071,000.00 Registration phase No registration expected Product Active substance Nivolumab Domain Oncology and Hematology Reason of inclusion Indication extension IND Main indication Lung cancer Extended indication Extension of Indication to include first-line treatment of adult patients with metastatic Non-Small Cell Lung Carcinoma (NSCLC) in combination with ipilimumab. Current proprietary name Already available biosimilars / generics Proprietary name Opdivo Manufacturer BMS Portfolio holder Mechanism of action PD-1 / PD-L1 inhibitor Route of administration Intravenous Therapeutical formulation Intravenous drip Budgetting framework Intermural (MSZ) Centre of expertise Additional remarks PD-1 remmer. Financieel arrangement van toepassing op alle indicaties. Registration Registration route Centralised (EMA) Type of trajectory Normal trajectory Particularity Unknown ATMP Unknown Submission date May 2018 Expected Registration Orphan drug No Registration phase No registration expected Reimbursement Medicine sluice Additional remarks Checkmate 227; met PFS primary endpoint in high tumor burden. In februari 2020 is de registratie bij de EMA teruggetrokken door BMS. De CHMP kon op basis van de data geen goede assessment uitvoeren. BMS is niet van plan deze registratieaanvraag opnieuw in te dienen maar zal zich focussen op de combinatie nivolumab, ipilimumab en chemotherapie voor deze indicatie. Therapeutic value Current treatment options Platinum doublet chemo, pembrolizumab (PDL1 ≥ 50%), pembrolizumab + chemo. Binnenkort: atezolizumab + bevacizumab + chemo (PDL1 all comers), atezolizumab + chemo Therapeutic value No judgement This assessment does not indicate any potential inclusion in the package. Substantiation Studieresultaten: wel een verschil in PFS maar geen verschil in OS, biomarker (tumour mutational load) daarnaast nog niet mogelijk in Nederland. Duration of treatment Median 4.2 Not found Frequency of administration 1 times every 2 weeks Dosage per administration 3 mg/kg References https://news.bms.com/press-release/bms/pivotal-phase-3-checkmate-227-study-demonstrates-superior-progression-free-surviva; Hellmann et al. N Engl J Med 2018; 378:2093-2104; NCT02477826 https://www.ema.europa.eu/en/documents/withdrawal-report/withdrawal-assessment-report-opdivo-yervoy-ws/1372_en.pdf Additional remarks Opdivo 3 mg/kg every two weeks and low-dose Yervoy (1 mg/kg) every six weeks. Median duration of treatment is 4,2 maanden Expected patient volume per year Patient volume < 1,193 Market share is generally not included unless otherwise stated. Maximum patient volume for sluice References NKR 2016, GIP-databank; Hellmann et al. N Engl J Med 2018; 378:2093-2104 Additional remarks Jaarlijks presenteren er ongeveer 4.500 patiënten per jaar met NSCLC stadium IV. Hiervan zal 60% een eerstelijnsbehandeling krijgen (2.700). Hoog tumor mutational burden (TMB ≥ 10 mutaties per megabase) komt bij 44.2% van patiënten voor. Hierdoor komen 1.193 patiënten in aanmerking voor behandeling met nivolumab in combinatie met ipilimumab. De biomarker die nodig is is echter nog niet overal beschikbaar in Nederland. Expected cost per patient per year Cost € 47,000.00 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 G-standaard, januari 2019; Hellmann et al. N Engl J Med 2018 Additional remarks Ipilimumab 50 mg kost €4.250, ipilimumab 2.000 mg kost €17.000,00. Bij een behandelduur van 4,2 maanden worden 9 toedieningen Opdivo gebruikt: €21.871,00 (9 x €2.430,00) en 3 toedieningen Yervoy: €25.500,00 (3 x €8.500,00). In totaal bedraagt dit €47.371,00. Voor alle indicatie van nivolumab geldt een financieel arrangement die is voortgekomen uit de onderhandelingen in de sluis (lopend tot eind 2020). Potential total cost per year Total cost € 56,071,000.00 Total cost for sluice Additional remarks Off label use Off label use Unknown Indications off label use References Additional remarks Indication extension Indication extensions Yes Indication extensions Buiten de indicaties in de Horizonscan geen nieuwe indicatie-uitbreidingen bekend. References adisinsight Additional remarks Other information Additional remarks