Ivosidenib Versus Chemotherapy for Previously Treated IDH1mutant Advanced Intrahepatic Cholangiocarcinoma in Taiwan Presenter Kuei An Andy Chen MS Team members WM Huang E Chen PK Ho NJ Chiang YW Tsai ID: 1009491
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1. Cost-Effectiveness Analysis of Ivosidenib Versus Chemotherapy for Previously Treated IDH1-mutant Advanced Intrahepatic Cholangiocarcinoma in TaiwanPresenter: Kuei-An (Andy) Chen, MSTeam members: WM Huang, E Chen, PK Ho, NJ Chiang, YW TsaiAffiliation: National Yang Ming Chiao Tung University (NYCU)Date: 2023/05/081
2. DisclaimersI do have NO affiliations with or involvement in any organization or entity with any financial interest, or non-financial interest in the subject matter or materials discussed in this presentation.
3. OutlineIntroductionMethodsResultsConclusions3
4. Introduction4
5. IntroductionCCA is a rare and severe cancer worldwide, with a higher incidence in AsiaCCA: cholangiocarcinoma, iCCA: intrahepatic CCA, pCCA: perihilar CCA, dCCA: distal CCA1 Banales et al., 20162 Banales et al., 2020Incidence rate1:< 6/100,000 in most countries< 3/100,000 in most Western countriesRareIncidence rate1:> 7/100,000 in China, South Korea, and Thailand4.7/100,000 in TaiwanAsian70% are diagnosed already in advanced stages2SevereDisease OverviewTreatmentsTreatment for IDH1 mutationsTreatment under NHI TaiwanObjectivesiCCA(10-20%)pCCA(50-60%)dCCA(20-30%)
6. IntroductionSystemic therapies for patients with advanced CCA and ICCCCA: cholangiocarcinoma, FOLFOX: fluorouracil + leucovorin + oxaliplatin, ICC: intrahepatic cholangiocarcinomaMSI-H: microsatellite instability-high, dMMR: mismatch repair deficient, TMB-H: tumor mutational burden-high, BRAF:FGFR2: fibroblast growth factor receptor 2, HER2: human epidermal growth factor receptor 2, IDH1: isocitrate dehydrogenase 1, NTRK: neurotrophic tyrosine receptor kinase,1 NCCN (https://www.nccn.org/professionals/physician_gls/pdf/btc.pdf), 2 Vogel et al., 2023Chemo-therapy1, 21st line treatment:Gemcitabine + cisplatin ± durvalumabSubsequent treatment:Modified FOLFOXNTRK<1%MSI-H/dMMR1%-3%TMB-H<5%RET<1%IDH110%-20% in ICCBRAF V600E1%-5%HER25%-20%FGFR29%-15% in ICCTargeted therapy1, 2Disease OverviewTreatmentsTreatment for IDH1 mutationsTreatment under NHI TaiwanObjectivesOnly for subsequent treatment
7. IntroductionIvosidenib is an effective but expensive treatment for previously treated advanced ICC patients with IDH1 mutationsUSD: the US dollar, NTD: National Taiwan dollarCCA: cholangiocarcinoma, ICC: intrahepatic cholangiocarcinoma, IDH1: isocitrate dehydrogenase-11 Abou-Alfa et al., 2020, 2 Zhu et al., 2021, 3 FDA, 4 NCCN, 5 Vogel et al., 2023, 6 Red Book OnlineA placebo-controlled, phase III trial, >90% advanced ICCmPFS: 2.7 vs 1.4 months (HR: 0.37; 95% CI: 0.25-0.54)mOS: 10.3 vs 5.1 months (HR: 0.49; 95% CI: 0.34-0.70)ClarIDHy trial1, 2Both NCCN and ESMO recommended ivosidenib as a subsequent treatment for advanced CCA patients with IDH1 mutations Guideline4, 5FDA approved ivosidenib as the treatment of patients with previously treated locally advanced or metastatic CCA and IDH1 mutations (2021/8)FDA3Treatment for IDH1 mutations:“IVOSIDENIB”36,051 USD per 28-day cycle (1,074,687 NTD) 6Disease OverviewTreatmentsTreatment for IDH1 mutationsTreatment under NHI TaiwanObjectives
8. IntroductionThe value of ivosidenib was uncertain due to the efficacy seemed to be worse than pemigatinib and had a 3-time higher costNHI: national health insurance, 5FU/LV: fluorouracil + leucovorin, FGFR2: fibroblast growth factor receptor 2, IDH1: isocitrate dehydrogenase 11 National Health Insurance Administration. 2 Abou-alfa et al., 2020, 3 Lamarca et al., 2021, 4 Yoo et al., 2021.IvosidenibPemigatinib2mFOLFOX35FU/LV4TrialClarIDHyFIGHT-2022ABC-063NIFTY4GenotypeIDH-1FGFR2wildtypewildtypeOS (months)10.321.16.25.5PFS (months)2.76.94.01.4Taiwan NHI listing1XO (May 2023)XO28-day cycle cost36,051 USD 1,074,687 NTD12,399 USD369,600 NTD346 USD10,322 NTD68 USD2,032 NTDDisease OverviewTreatmentsTreatment for IDH1 mutationsTreatment under NHI TaiwanObjectives
9. IntroductionAims to evaluate the cost-effectiveness of ivosidenib in previously treated IDH1-mutant advanced ICC patients compared with mFOLFOX or 5-FU/LV chemotherapy regimens from the Taiwan NHI’s perspective.Currently, no CEA on ivosidenib for the targeted populationProvide CEA evidence and identify the optimal ceiling priceDisease OverviewTreatmentsTreatment for IDH1 mutationsTreatment under NHI TaiwanObjectiveIvosidenib5FU/LVmFOLFOXVS9
10. Methods10
11. MethodsModel constructionPartitioned survival model (PSM)Study populationPreviously treated adult IDH1-mutant advanced ICC patientsInterventionsIvosidenibComparisonmFOLFOX5-FU/LVOutcomesICER, NMBStates3 states (progression-free, post-progression, death)Time horizon 10 yearsCycle length4 weeks/cycleDiscount rate3%PerspectivePayer perspective (National Health Insurance Administration)WTP3*GDP (2022 Taiwan)/QALY = 2,928,570 NTD/QALY (98,241 USD/QALY)Model constructionPartitioned survival model (PSM)Study populationPreviously treated adult IDH1-mutant advanced ICC patientsInterventionsIvosidenibComparisonmFOLFOX5-FU/LVOutcomesStates3 states (progression-free, post-progression, death)Time horizon 10 yearsCycle length4 weeks/cycleDiscount rate3%PerspectivePayer perspective (National Health Insurance Administration)WTP3*GDP (2022 Taiwan)/QALY = 2,928,570 NTD/QALY (98,241 USD/QALY)Model overviewParametersCost-effectiveness analysisICER: incremental cost-effectiveness ratio, NMB: delta net monetary benefit
12. MethodsThe mixture survival curves of KM and parametric curves for both PFS and OSTrialOSPFSIvosidenibClarIDHy10.32.7mFOLFOXABC-066.24.05FU/LVNIFTY5.51.4R softwareParametric distributionsBest-fitting2:AIC, BIC, Visual assessmentlog-normallog-logisticexponentialWeibullgammageneralized gammaGompertzRCTPseudo IPD1Parametric survival modelSurvival model parametersModel overviewParameters – EfficacyCost-effectiveness analysis1 WebPlotDigitizer v4.6, 2 Guyot et al., 2012
13. MethodsA price ratio between the US AWP and TW NHI fee in pemigatinib was used to estimate the price of ivosidenibPemigatinib1US AWPPemigatinib2NHI feeRatioIvosidenib1US AWPExpected IvosidenibNHI feeRatioExchange rate: 29.81, AWP: annual wholesales price1 Red Book Online, 2 National Health Insurance Administration.Model overviewParameters – Medication costCost-effectiveness analysisIvosidenib1, 215,473 USD461,239 NTDmFOLFOX2346 USD10,322 NTD5FU/LV268 USD2,032 NTD28-day cycle costPrice of ivosidenib
14. MethodsThe parameters from our previous study targeted the same population, which was estimated by using a population-based claimed databaseExchange rate: 29.811 Chueh et al., 2022.Model overviewParameters – Non-medication costCost-effectiveness analysisIvosidenib1750 USD22,367 NTDChemotherapy12,205 USD65,741 NTDProgression-free stateSupportive care1346 USD10,322 NTDPost-progression state28-day cycle cost28-day cycle cost
15. MethodsUtilities were based on the setting of the NICE report (TA722, TA427), as our previous study1 Chueh et al., 2022. 2 NICE (TA722), 3 NICE (TA427), Model overviewParameters – UtilityCost-effectiveness analysisProgression-free state1, 20.76Post-progression state1, 20.68Health state utilityIntravenous therapy1, 3-0.025Grade 3 and higher AEs1, 2, 3 -0.16Disutility
16. MethodsModel overviewParametersCost-effectiveness analysisBase caseIncremental cost-effectiveness ratio (ICER)net monetary benefit (NMB) Deterministic sensitivity analysis±25% change from the base-case valueProbability analysisMonte Carlo simulation of 1,000 iterationsScenario analysis50% to 30% cost down
17. Results17
18. ResultsThe ICER of ivosidenib compared to the mFOLFOX or 5FU/LV regimens were more than the WTP*decision criteria：ICER < WTP(2,928,570 NTD/QALY, 98,241 USD/QALY) or ΔNMB>0ItemsCost(NTD)Cost(NTD)QALYsQALYsICER(NTD)NMB(NTD)InterventionIvosidenib4,368,9070.92Comparator 1mFOLFOX599,0853,769,8220.530.399,670,485-2,628,185Comparator 25FU/LV466,1763,902,7320.470.458,664,634-2,583,643ItemsCost(NTD)QALYsICER(NTD)InterventionIvosidenib4,368,9070.92Comparator 1mFOLFOX599,0853,769,8220.530.399,670,485-2,628,185Comparator 25FU/LV466,1763,902,7320.470.458,664,634-2,583,643Base caseProbability analysisTornado diagramScenario analysisItemsCost(USD)Cost(USD)QALYsQALYsICER(USD)NMB(USD)InterventionIvosidenib146,5580.92Comparator 1mFOLFOX20,097126,4610.530.39324,404-88,165Comparator 25FU/LV15,638130,9200.470.45290,662-86,670ItemsCost(USD)QALYsICER(USD)InterventionIvosidenib146,5580.92Comparator 1mFOLFOX20,097126,4610.530.39324,404-88,165Comparator 25FU/LV15,638130,9200.470.45290,662-86,670
19. ResultsIvosidenib was found to be 0.1% cost-effective compared with mFOLFOX or 5FU/LV under the WTPWTP= 2,928,570 NTD/QALY, 98,241 USD/QALY99.9%Base caseProbability analysisTornado diagramScenario analysis0.1%99.9%0.1%
20. ResultsThe medication cost and the health state utility were the most sensitive parameters to ICER changesBase caseProbability analysisTornado diagramScenario analysisIvosidenib vs 5FU/LV regimenIvosidenib vs mFOLFOX regimen
21. ResultsIvosidenib becomes cost-effective with a 70% price down *decision criteria：ICER < WTP(2,928,570 NTD/QALY, 98,241 USD/QALY) or ΔNMB>0Base caseProbability analysisTornado diagramScenario analysisIvosidenib vs mFOLFOXIvosidenib vs 5-FU/LVScenario (NTD)ICERNMBICERNMBBase-case (NT$16,473 per 500 mg)9,670,485-2,628,1858,664,634-2,583,64350% price of ivosidenib (NT$8,237 per 500 mg) 4,715,642-696,6504,376,345-652,10840% price of ivosidenib (NT$6,589 per 500 mg) 3,724,624-310,3433,518,688-265,80130% price of ivosidenib (NT$4,942 per 500 mg) 2,733,70575,9642,661,030120,506Ivosidenib vs mFOLFOXIvosidenib vs 5-FU/LVScenario (NTD)ICERICERBase-case (NT$16,473 per 500 mg)9,670,485-2,628,1858,664,634-2,583,64350% price of ivosidenib (NT$8,237 per 500 mg) 4,715,642-696,6504,376,345-652,10840% price of ivosidenib (NT$6,589 per 500 mg) 3,724,624-310,3433,518,688-265,80130% price of ivosidenib (NT$4,942 per 500 mg) 2,733,70575,9642,661,030120,506Ivosidenib vs mFOLFOXIvosidenib vs 5-FU/LVScenario (USD)ICERNMBICERNMBBase-case (US$553 per 500 mg)324,404-88,165290,662-86,67050% price of ivosidenib (US$276 per 500 mg) 158,190-23,370146,808-21,87640% price of ivosidenib (US$221 per 500 mg) 124,946-10,411118,037-8,91730% price of ivosidenib (US$166 per 500 mg) 91,7042,54889,2664,042Ivosidenib vs mFOLFOXIvosidenib vs 5-FU/LVScenario (USD)ICERICERBase-case (US$553 per 500 mg)324,404-88,165290,662-86,67050% price of ivosidenib (US$276 per 500 mg) 158,190-23,370146,808-21,87640% price of ivosidenib (US$221 per 500 mg) 124,946-10,411118,037-8,91730% price of ivosidenib (US$166 per 500 mg) 91,7042,54889,2664,042
22. Conclusions22
23. ConclusionsIvosidenib was not cost-effective compared with mFOLFOX or 5FU/LV in IDH1-mutant previously treated advanced ICC patients from the Taiwan NHI’s perspective.Ivosidenib needs a 70% price reduction (4,942 NTD/ 500mg; 166 USD/ 500mg) to become cost-effective when compared with both mFOLFOX and 5FU/LV.70% ↓
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25. Thank you!e-mail: andy061677@gmail.comLinkedIn: Kuei-An (Andy) Chen25