Cost-effectiveness of gilteritinib for relapsed/refractory FLT3mut+ acute myeloid leukemia.

BACKGROUND: Patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) and confirmed feline McDonough sarcoma (FMS)-like tyrosine kinase 3 gene mutations (FLT3mut+) have a poor prognosis and limited effective treatment options. Gilteritinib is the first targeted therapy approved in the United States and Europe for R/R FLT3mut+ AML with significantly improved efficacy compared with existing treatments. OBJECTIVE: To evaluate gilteritinib against salvage chemotherapy (SC) and best supportive care (BSC) over a lifetime horizon among adult patients with R/R FLT3mut+ AML from a US third-party payer's perspective. METHODS: The model structure of this cost-effectiveness analysis included a decision tree to stratify patients based on their hematopoietic stem cell transplantation (HSCT) status, followed by 2 separate 3-state partitioned survival models to predict the long-term health status conditional on HSCT status. The ADMIRAL trial data and literature were used to predict probabilities of patients being in different health states until a conservative cure point at year 3. Afterwards, living patients followed the survival outcomes of long-term survivors with AML. Model inputs for utilities, medical resource use, and costs were based on the ADMIRAL trial, published literature, and public sources. All costs were inflated to 2019 US dollars (USD). Total incremental costs (in 2019 USD), life-years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated. Deterministic sensitivity analyses and probabilistic sensitivity analyses were performed. RESULTS: Over a lifetime horizon with a 3.0% annual discount rate, the base-case model estimated that gilteritinib led to an increase of 1.29 discounted QALYs at an additional cost of $148,106 vs SC, corresponding to an ICER of $115,192 per QALY; for BSC, results were an increase of 2.32 discounted QALYs, $249,674, and $107,435, respectively. The base-case findings were robust in sensitivity analyses. The estimated probabilities of gilteritinib being cost-effective vs SC and BSC were 90.5% and 99.8%, respectively, in the probabilistic sensitivity analyses, based on a willingness-to-pay threshold of $150,000 per QALY. CONCLUSIONS: Gilteritinib is a cost-effective novel treatment for patients with R/R FLT3mut+ AML in the United States. DISCLOSURES: This work was supported by Astellas Pharma, Inc., which was involved in all stages of the research and manuscript development. Garnham, Pandya, and Shah are employees of Astellas and hold stock/stock options. Zeidan consulted and received personal fees/honoraria and research funding from Astellas. Zeidan also has received research funding from Celgene/BMS, Abbvie, Astex, Pfizer, Medimmune/AstraZeneca, Boehringer-Ingelheim, Trovagene/Cardiff Oncology, Incyte, Takeda, Novartis, Amgen, Aprea, and ADC Therapeutics; has participated in advisory boards; has consulted with and/or received honoraria from AbbVie, Otsuka, Pfizer, Celgene/BMS, Jazz, Incyte, Agios, Boehringer-Ingelheim, Novartis, Acceleron, Daiichi Sankyo, Taiho, Seattle Genetics, BeyondSpring, Cardiff Oncology, Takeda, Ionis, Amgen, Janssen, Syndax, Gilead, Kura, Aprea, Lox Oncology, Genentech, Servier, Jasper, Tyme, and Epizyme; has served on clinical trial committees for Novartis, Abbvie, Geron, Gilead, Kura, Lox Oncology, BioCryst, and Celgene/BMS; and has received travel support for meetings from Pfizer, Novartis, and Cardiff Oncology. Qi and Yang are employees of Analysis Group, Inc., which received consulting fees from Astellas for work on this study. Part of this material was presented at the American Society of Hematology (ASH) Annual Meeting; December 7-10, 2019; Orlando, FL.

Cost-effectiveness analysis of first-line treatments for advanced epidermal growth factor receptor-mutant non-small cell lung cancer patients.

OBJECTIVES: Recent studies showed prolonged survival for advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients treated with both monotherapies and combined therapies. However, high costs limit clinical applications. Thus, we conducted this cost-effectiveness analysis to explore an optimal first-line treatment for advanced EGFR-mutant NSCLC patients. MATERIALS AND METHODS: Survival data were extracted from six clinical trials, including ARCHER1050 (dacomitinib vs. gefitinib); FLAURA (osimertinib vs. gefitinib/erlotinib); JO25567 and NEJ026 (bevacizumab +erlotinib vs. erlotinib); NEJ009 (gefitinib +chemotherapy vs. gefitinib); and NCT02148380 (gefitinib +chemotherapy vs. gefitinib vs. chemotherapy) trials. Cost-related data were obtained from hospitals and published literature. The effect parameter (quality-adjusted life year [QALY]) was the reflection of both survival and utility. Incremental cost-effectiveness ratio (ICER), average cost-effectiveness ratio (ACER), and net benefit were calculated, and the willingness-to-pay (WTP) threshold was set at $30828/QALY from the perspective of the Chinese healthcare system. Sensitivity analysis was performed to explore the stability of results. RESULTS: We compared treatment groups with control groups in each trial. ICERs were $1897750.74/QALY (ARCHER1050), $416560.02/QALY (FLAURA), -$477607.48/QALY (JO25567), -$464326.66/QALY (NEJ026), -$277121.22/QALY (NEJ009), -$399360.94/QALY (gefitinib as comparison, NCT02148380), and -$170733.05/QALY (chemotherapy as comparison, NCT02148380). Moreover, ACER and net benefit showed that the combination of EGFR-TKI with chemotherapy and osimertinib was of more economic benefit following first-generation EGFR-TKIs. Sensitivity analyses showed that the impact of utilities and monotherapy could be cost-effective with a 50% cost reduction. CONCLUSION: First-generation EGFR-TKI therapy remained the most cost-effective treatment option for advanced EGFR-mutant NSCLC patients. Our results could serve as both a reference for both clinical practice and the formulation of medical insurance reimbursement.

Incremental cost-effectiveness analysis of tyrosine kinase inhibitors in advanced non-small cell lung cancer with mutations of the epidermal growth factor receptor in Colombia.

OBJECTIVE: To estimate the cost-effectiveness of sequences starting with tyrosine kinase inhibitors (TKI), afatinib and osimertinib, for the treatment of epidermal growth factor receptor (EGFR) mutation-positive (Exon 19 deletion or L858R) non-small cell lung cancer (NSCLC), stages IIIB - IV in Colombia. METHODS: A partitioned survival model was designed, using information from global and progression-free survival curves. For first and second-generation TKI, second line treatment was assumed according to the presence of T790M mutation to define the use of osimertinib or chemotherapy. The cost of the states without progression and post-progression was estimated using the base case approach, identified through consultation with clinical experts. RESULTS: The cost of treatment starting with afatinib in the first line was of 222,247 USD (1 USD = 3171.99 COP) and produced 1.36 QALYs. The strategy with afatinib was dominant with respect to that of first line TKI (227,289 USD and 1.34 QALY). The strategy with osimertinib resulted in more QALYs and higher costs, with ICERs of 35,062 USD, exceeding the current willingness to pay threshold for Colombia. CONCLUSIONS: Treatment starting with afatinib in the first line is dominant with respect to the strategy with first line TKI. The ICER of osimertinib sequence exceeds the threshold when compared with afatinib one.

Cost-effectiveness of osimertinib versus standard EGFR-TKI as first-line treatment for locally advanced or metastatic EGFR mutation-positive non-small cell lung cancer in Australia.

Objectives: To assess the cost-effectiveness of osimertinib versus standard epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), gefitinib or erlotinib, as first-line treatment for patients with locally advanced or metastatic EGFR mutation-positive non-small cell lung cancer in Australia from a healthcare system perspective.Methods: A partitioned survival model comprising three mutually exclusive health states with a five-year time horizon was developed. Model inputs were sourced from the pivotal trial (FLAURA) and published literature. Incremental cost-effectiveness ratios (ICERs), in terms of cost per quality-adjusted life-year (QALY) gained and cost per life-year (LY) gained, were calculated. Uncertainty of the results was assessed using deterministic and probabilistic sensitivity analyses.Results: Compared with standard EGFR-TKIs, osimertinib was associated with a higher incremental cost of A$118,502, and an incremental benefit of 0.274 QALYs and 0.313 LYs. The ICER was estimated to be A$432,197/QALY gained and A$378,157/LY gained. The base-case ICER was most sensitive to changes in cost of first-line osimertinib, time horizon, and choice of overall survival data (interim versus final analysis).Conclusions: At a willingness-to-pay threshold of A$50,000/QALY, first-line osimertinib is not cost-effective compared with standard EGFR-TKIs in Australia based on the current published price. To achieve acceptable cost-effectiveness, the cost of first-line osimertinib needs to be reduced by at least 68.4%.

Cost-effectiveness analysis of osimertinib for first-line treatment of locally advanced or metastatic EGFR mutation positive non-small cell lung cancer in Singapore.

OBJECTIVE: Non-small cell lung cancer (NSCLC) accounts for 80-90% of all lung cancer cases and is usually associated with a poor prognosis. However, targeted therapy with first and second generation tyrosine kinase inhibitors (TKIs) has so far improved progression-free survival of epidermal growth factor receptor (EGFR) mutant NSCLC patients. Osimertinib, a third generation EGFR TKI has recently shown improved overall survival of 6.8 months in previously untreated EGFR mutant NSCLC patients. We assessed the cost-effectiveness of osimertinib versus standard EGFR TKIs (gefitinib or erlotinib) as first-line treatment for advanced or metastatic EGFR mutant NSCLC patients in Singapore. METHODS: A partitioned survival model with three health states (progression-free, progressive disease, and death) was developed from the Singapore healthcare payer perspective. Survival curves based on the overall trial population from the FLAURA trial were extrapolated beyond trial period over a 10-year time horizon to estimate the underlying progression-free survival and overall survival parametric distributions. Health state utilities were derived from the literature and direct costs were sourced from public healthcare institutions in Singapore. Deterministic and probabilistic sensitivity analyses were conducted to explore the impact of uncertainties and assumptions on cost-effectiveness results. RESULTS: Compared with first or second generation TKI, osimertinib had a base-case incremental cost-effectiveness ratio (ICER) of SG$418,839 (US$304,277) per quality-adjusted life year gained. One-way sensitivity analysis showed the ICER was most sensitive to time horizon and variations in progression-free utility values. Scenario analyses showed that a 50% reduction in the cost of osimertinib was still associated with a high ICER that was unlikely to be deemed cost effective. CONCLUSIONS: Osimertinib is not cost effective as a first-line treatment compared to standard EGFR TKIs in advanced EGFR mutant NSCLC patients in Singapore. The findings from our evaluation, alongside other considerations including the lack of survival benefit in the Asian subgroup of the FLAURA trial, will be useful to inform policy makers on funding decisions for NSCLC treatments in Singapore.

Pricing methods in outcome-based contracting: δ3: reference-based pricing.

AIMS: Six Delta is a six-dimensional independent platform for outcome-based pricing/contracting. The third dimension (δ3) estimates prices on the basis of international drug price referencing methods. We describe this dimension's methodology and present a proof-of-concept application to the treatment of non-small cell lung cancer (NSCLC) with EGFR mutation with osimertinib. MATERIALS AND METHODS: The reference-based pricing dimension utilizes a six-step method: (1) selecting foreign countries based on a set of four criteria (drug is available in the foreign country, price information is available in the foreign country, foreign countries are members within the organization for Economic Co-operation and Development, pricing methods in the foreign countries involve value assessment); (2) adjusting for exchange rates; (3) generating reference price (RP) scenarios; (4) adjusting with the medical inflation rate; (5) pooling all generated RP scenarios and calculating average and standard deviation (SD); (6) and Monte Carlo Simulation (MCS) to estimate the dimension-specific DSPReference. A proof-of-concept exercise with osimertinib in NSCLC was performed for two hypothetical outcome-based contracts: 1-year (2019-2020) and 2-year (2019-2021). RESULTS: The United Kingdom and Canada met the four criteria. For the osimertinib 1-year contract price, the average of eight RP scenarios, adjusted for inflation by 0.44%, was $8,892 (SD = $2,606) for a 30-day prescription. MCS yielded a DSPReference estimate of $9,395 or -35.72% of the wholesale acquisition cost (WAC) of $14,616. For the 2-year contract, the average, adjusted for inflation by 0.72%, was $8,928 (SD = $2,610). MCS yielded a DSPReference estimate of $9,442 or -35.40% of the WAC of $14,616. CONCLUSIONS: We demonstrated that international price referencing methods can be integrated into our proposed Six Delta platform for outcome-based pricing/contracting.

Pricing methods in outcome-based contracting: δ2: willingness-to-pay-based pricing.

AIMS: Six Delta is a six-dimensional independent platform for outcome-based pricing/contracting. The second dimension (δ2) estimates prices on the basis of four willingness-to-pay (WTP) thresholds. We describe this dimension's methodology and present a proof-of-concept application to the treatment of non-small cell lung cancer (NSCLC) with EGFR mutation with osimertinib. MATERIALS AND METHODS: Eight WTP scenarios based on four levels of real gross domestic product per capita (<1GDP/capita, 1 × GDP/capita, 3 × GDP/capita, and >3 × GDP/capita) and two market conditions (monopolistic versus competitive) were assumed. The incremental cost-utility ratio (ICUR) was applied to differently to both markets. In the monopolistic market, assuming no competitors, the cost/QALY ratio for a drug was used; whereas in the competitive market, assuming competitors, the incremental cost-utility ratio (ICUR) was applied. One-way sensitivity analyses were performed and predictive equations were specified to estimate the prices of treatment for the resulting eight WTP scenarios; for which subsequently the average and standard deviation were calculated. A gamma distribution was specified and Monte Carlo Simulation (MCS) was applied to estimate the dimension-specific price based on WTP (DSPWTP). A proof-of-concept exercise with osimertinib in NSCLC was performed for two hypothetical outcome-based contracts: 1-year (2019-2020) and 2-year (2019-2021). The 2018 wholesale acquisition cost (WAC) of $14,616 (30-day prescription) was used to estimate the DSPWTP for each contract. RESULTS: The 1-year estimates averaged $4,654 (SD=$6,462) and the MCS yielded a DSPWTP of $4,547 or -68.89% of the 2018 WAC for a 30-day prescription. The 2-year estimates averaged $4,7667 (SD=$6,480) with the MCS generating a DSPWTP of $4,704 or -67.82% of the WAC. CONCLUSIONS: We demonstrated that WTP-based methods that include various WTP thresholds and market conditions generate price estimates across these thresholds and market conditions that can be integrated into our proposed Six Delta platform for outcome-based pricing/contracting.

Pricing methods in outcome-based contracting: δ4: safety-based pricing.

AIMS: Six Delta is a six-dimensional independent platform for outcome-based pricing/contracting. The fourth dimension (δ4) estimates prices on the basis of assessments of the safety of the drug using an ex ante analysis based on clinical trial data. We describe this dimension's methodology and present a proof-of-concept application to the treatment of non-small cell lung cancer (NSCLC) with EGFR mutation with osimertinib. MATERIALS AND METHODS: The safety-based pricing dimension utilizes a four-step method: 1) pooling adverse events (AE), standardizing, estimating 95%Cis, and adjusting for time; 2) estimating correction factors and corrected probabilities of AEs; 3) estimating the probability of at least one adverse event (AE) occurring and leading to treatment discontinuation; and 4) estimating ranges for payback percentages and performing Monte Carlo Simulation to estimate a DSPSafety. A proof-of-concept exercise with osimertinib in NSCLC was performed for two hypothetical outcome-based contracts: 1-year (2019-2020) and 2-year (2019-2021). We estimated the DSPSafety based on the grade 3/4 AEs observed for osimertinib and standard of care. The 2018 wholesale acquisition cost (WAC) of osimertinib at $14,616 for a 30-day prescription was used. RESULTS: AEs3/4 were retrieved from the FLAURA trial. In the 1-year contract, the DSPSafety of osimertinib was estimated at $14,627 (or +0.08% the 2018 WAC) for a 30-day prescription. In the 2-year contract, the DSPSafety of osimertinib was estimated at $14,516 (or -0.68% the 2018 WAC) for a 30-day prescription. CONCLUSIONS: We demonstrated that ex ante pricing methods-based paybacks for safety issues leading to treatment discontinuation can be integrated into our proposed Six Delta platform for outcome-based pricing/contracting.

Pricing methods in outcome-based contracting: δ5: risk of efficacy failure-based pricing.

AIMS: Six Delta is a six-dimensional independent platform for outcome-based pricing/contracting. The fifth dimension (δ5) estimates prices on the basis of the risk of efficacy failure of a drug. We describe this dimension's methodology and present a proof-of-concept application to the treatment of non-small cell lung cancer (NSCLC) with EGFR mutation with osimertinib. MATERIALS AND METHODS: The risk of efficacy failure pricing dimension utilizes a seven-step method: (1) defining risk; (2) extracting data; (3) predicting models; (4) performing Monte Carlo Simulation (MCS) to estimate risk of efficacy failure; 5) estimating ranges for a payback; (6) adjusting for medical inflation; and (7) performing Monte Carlo Simulation (MCS) to estimate the DSPRisk of efficacy failure. A proof-of-concept exercise with osimertinib in NSCLC was performed for two hypothetical outcome-based contracts: 1-year (2019-2020) and 2-year (2019-2021). We estimated the risk of efficacy failure for osimertinib in terms of overall and progression-free survival versus standard of care. We used the estimated risk to estimate the price reduction on the wholesale acquisition cost (WAC) for the two hypothetical contracts: a 1-year (2019-2020) and 2-year contract (2019-2021). From this we estimated the DSPRisk of efficacy failure. RESULTS: Based on the risk of OS and PFS efficacy failure for osimertinib in OS and PFS, in the 1-year contract, the DSPRisk of efficacy failure was estimated at $12,652 (or -13.44% the 2018 WAC) for a 30-day prescription. For the 2-year contract (2019-2021), the DSPRisk of efficacy failure was estimated at $13,019 (or -10.93% the 2018 WAC). CONCLUSIONS: We demonstrated that pricing methods based on risk of efficacy failure methods can be integrated into our proposed Six Delta platform for outcome-based pricing/contracting.

Pricing methods in outcome-based contracting: δ6: adherence-based pricing.

AIMS: Six Delta is a six-dimensional independent platform for outcome-based pricing/contracting. The sixth dimension (δ6) estimates prices on the basis of adherence to the prescribed regimen, whereby manufacturers provide payers with adherence-enhancing programs and whereby payers implement these programs and provide adherence data to the manufacturer. We describe this dimension's methodology and present a proof-of-concept application to the treatment of non-small cell lung cancer (NSCLC) with EGFR mutation with osimertinib. MATERIALS AND METHODS: We propose two paybacks based on adherence: in-advance (based on clinical trial data) and in-arrear (based on real-world data). The risk of efficacy failure pricing dimension utilizes a 7-step method: 1) defining efficacy endpoints; 2) extracting data; 3) predicting models; 4) estimating in-advance and in-arrear paybacks; 5) suggesting ranges for in-advance and in-arrear paybacks; 6) adjusting for medical inflation; and 7) performing Monte Carlo Simulation (MCS) to estimate the DSPAdherence. A proof-of-concept exercise with osimertinib in NSCLC was performed for two hypothetical outcome-based contracts: 1-year (2019-2020) and 2-year (2019-2021). The 2018 wholesale acquisition cost (WAC) for a 30-day prescription was used and inflated as needed. Herein, the DSPAdherence is estimated exclusively in terms of in-advance payback because real-world data about osimertinib are not yet available and thus the in-arrear payback cannot yet be estimated. RESULTS: For the 1-year contract, the average price for osimertinib was $13,798 (SD=$1,265) and the DSPAdherence was $13,785 (or -5.69% of the 2018 WAC) for a 30-day prescription. For the 2-year contract, the average price was $12,555 (SD=$2,847) and the DSPAdherence was $12,582 (or -13.92% of the 2018 WAC). CONCLUSIONS: We demonstrated that adherence-based pricing methods can be integrated into our proposed Six Delta platform for outcome-based pricing/contracting. The proof-of-concept exercise needs to be expanded with the in-arrear pricing method based on real world data to be secured.

Pricing methods in outcome-based contracting: δ1: cost effectiveness analysis and cost-utility analysis-based pricing.

AIMS: Six Delta is a six-dimensional independent platform for outcome-based pricing/contracting. The first dimension (δ1) estimates prices on the basis of cost-effectiveness (CEA) and cost-utility analysis (CUA). We describe this dimension's methodology and present a proof-of-concept application to the treatment of non-small cell lung cancer (NSCLC) with EGFR mutation with osimertinib. MATERIALS AND METHODS: CEA and CUA were performed using established methods. Probabilistic sensitivity analyses (PSA) were performed to generate cost-effectiveness acceptability curves (CEAC), specifically the PSA incremental cost-effectiveness (PSA ICER) and incremental cost-utility ratio generated CEACs (PSA ICUR). Price of treatment was estimated at three certainty levels (0%, turning point%, 100%). The marketed drug price at turning point was used to estimate prices at 0% and 100% certainty levels, as per PSA ICER and PSA ICUR-generated CEACs. The resulting prices were pooled, inflated, and simulated by Monte Carlo Simulation (MCS) methods to estimate the dimension-specific price based on CEA and CUA (DSPCEA/CUA). A proof-of-concept exercise with osimertinib in NSCLC was performed for two hypothetical outcome-based contracts: 1-year (2019-2020) and 2-years (2019-2021). RESULTS: Turning points were estimated at the 50% certainty level in both PSA ICER and ICUR-generated CEACS. At these points, the wholesale acquisition cost for osimertinib was $14,616 (30-day prescription); inflated by 0.44% for 1-year and by 0.72% for 2-year contracts. Additional prices at 0% and 100% certainty levels were quantified based on the PSA ICER and ICUR-generated CEACs. The MCS yielded a DSPCEA/CUA of $16,391 for the 1-year contract and a DSPCEA/CUA at $16,677 for the 2-year contract for a 30-day prescription. CONCLUSIONS: We demonstrated that conventional CEA and CUA methods generate price estimates at varying levels of certainty that can be integrated into our proposed Six Delta platform for outcome-based pricing/contracting.

Pricing methods in outcome-based contracting: integration analysis of the six dimensions (6 δs).

AIMS: Six Delta is a six-dimensional independent platform for outcome-based pricing/contracting. The six dimensions have been described separately: (δ1) cost-effectiveness analysis and cost-utility analysis-based pricing; (δ2) willingness-to-pay-based pricing; (δ3) reference-based pricing; (δ4) safety-based pricing; (δ5) risk of efficacy failure-based pricing; and (δ6) adherence-based pricing. The final step is to integrate the various dimension-specific pricing estimates into a composite estimate termed the All-Dimensional Price (ADP). We describe the methodology for this integration and present a proof-of-concept application to the treatment of non-small cell lung cancer (NSCLC) with EGFR mutation with osimertinib. MATERIALS AND METHODS: For better accuracy in estimating the ADP, we used the prices generated from the six dimensions at scenario levels, not at the dimension-specific price (DSP) level. We pooled the price estimates and performed Monte Carlo Simulations (MCS) for the price scenarios generated by the six dimensions. We used the results of the proof-of-concept exercise involving osimertinib in NSCLC with EGFR mutation to estimate the ADP in two hypothetical contracts: 1-year (2019-2020) and 2-year contract (2019-2021). RESULTS: The average of the 30-day prescription estimates from the six dimensions averaged $10,819 (SD=$8,486) for the 1-year contract and $10,730 (SD=$8,500) for the 2-year contract. MCS yielded for the 1-year contract an ADP of $10,959 (or -25.02% the 2018 WAC price) and an ADP for the 2-year contract was $10,788 (or -26.19% the 2018 WAC price). CONCLUSIONS: We demonstrated that the integration of the prices from the six dimensions of the Six Delta platform and market conditions is feasible and yields multidimensional prices estimates to support outcome-based pricing/contracting.

Budget impact of sequential treatment with first-line afatinib versus first-line osimertinib in non-small-cell lung cancer patients with common EGFR mutations.

BACKGROUND: The therapeutic landscape for non-small-cell lung cancer (NSCLC) patients that have common epidermal growth factor receptor (EGFR) mutations has changed radically in the last decade. The availability of these treatment options has an economic impact, therefore a budget impact analysis was performed. METHODS: A budget impact analysis was conducted from a Dutch healthcare perspective over a 5-year time horizon in EGFR-mutant NSCLC patients receiving first-line afatinib (Gilotrif®) versus first-line osimertinib (Tagrisso®), followed by subsequent treatments. A decision analysis model was constructed in Excel. Scenario analyses and one-way sensitivity analysis were used to test the models' robustness. RESULTS: Sequential treatment with afatinib versus first-line treatment with osimertinib showed mean total time on treatment (ToT) of 29.1 months versus 24.7 months, quality-adjusted life months (QALMs) of 20.2 versus 17.4 with mean cost of €108,166 per patient versus €143,251 per patient, respectively. The 5-year total budget impact was €110.4 million for the afatinib sequence versus €158.6 million for the osimertinib sequence, leading to total incremental cost savings of €48.15 million. CONCLUSIONS: First-line afatinib treatment in patients with EGFR-mutant NSCLC had a lower financial impact on the Dutch healthcare budget with a higher mean ToT and QALM compared to osimertinib sequential treatment.

Cost-effectiveness of Osimertinib as a Second-line Treatment in Patients With EGFR-mutated Advanced Non-Small Cell Lung Cancer in China.

PURPOSE: To assess the cost-effectiveness of osimertinib used as a second-line treatment after failure of epidermal growth factor receptor tyrosine kinase inhibitor therapy for advanced non-small cell lung cancer (NSCLC) in China. METHODS: From the perspective of China's health care system, a Markov model was used for estimating the costs and health outcomes of osimertinib and 4 platinum-based chemotherapies, including pemetrexed + platinum (PP), gemcitabine + platinum (GP), docetaxel + platinum (DP), and paclitaxel + platinum (TP). Two scenarios were considered, one in all confirmed patients with T790M-positive disease (scenario 1) and the other in all patients whose disease progressed after epidermal growth factor receptor tyrosine kinase inhibitor therapy, which consisted of patients with T790M-positive or T790M-negative NSCLC (scenario 2). Clinical data for transition probabilities and treatment effects were obtained from published clinical trials. Health care resource utilization and costs were derived from local administrative databases and published literature. Deterministic and probabilistic sensitivity analyses were conducted to assess the uncertainty of the results. FINDINGS: In the base-case analysis, compared with the 4 platinum-based chemotherapies, osimertinib yielded an additional 0.671 to 0.846 quality-adjusted life-year (QALY), with incremental costs of 15,943 to 20,299 USD in scenario 1, and an additional 0.376 to 0.808 QALY with incremental costs of 9710 to 15,407 USD in scenario 2. In the probabilistic sensitivity analysis, the probabilities that osimertinib would be cost-effective were 57.7% in scenario 1 and 58.4% in scenario 2 if the willingness-to-pay threshold were 30,000 USD/QALY, and probabilities would be more than 75 % in both scenarios if the willingness-to-pay threshold were 50,000 USD/QALY. IMPLICATIONS: Osimertinib is likely to be cost-effective when used as a second-line treatment of advanced NSCLC in China based on the latest reimbursement price of osimertinib through National Reimbursement Drug List negotiation.

Osimertinib in first-line treatment of advanced EGFR-mutated non-small-cell lung cancer: a cost-effectiveness analysis.

Aim: Osimertinib improves progression-free survival in first-line EGFR mutation-positive non-small-cell lung cancer. Materials & methods: A Markov cohort model including costs, utilities and disutilities, was conducted to estimate quality-adjusted life-year (QALY) and incremental cost-effectiveness ratio when treating with osimertinib versus standard first-line tyrosine kinase inhibitors (TKIs). Results: Osimertinib presented higher QALYs (0.61) compared with standard EGFR-TKIs (0.42). Osimertinib costs were €83,258.99, in comparison with €29,209.45 for the standard EGFR-TKIs. An incremental cost-effectiveness ratio of €273,895.36/QALY was obtained for osimertinib. Conclusion: Osimertinib was more effective in terms of QALYs gained than comparators (erlotinib-gefitinib). However, to obtain a cost-effectiveness alternative, a discount greater than 60% in osimertinib acquisition cost is required.

Cost-effectiveness of Osimertinib as First-line Treatment and Sequential Therapy for EGFR Mutation-positive Non-small Cell Lung Cancer in China.

PURPOSE: This study aimed to evaluate the cost-effectiveness of osimertinib with gefitinib or erlotinib as first-line and sequential therapy for epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) in China. METHODS: The Markov model was used, and the study included 3 health states over a 10-year period. Transition probabilities and safety data were collected from the FLAURA (AZD9291 versus gefitinib or erlotinib in patients with locally advanced or metastatic Non-small Cell Lung Cancer) trial. Cost and utility values were derived from local charges and literature. Sensitivity analyses were performed to observe model stability. FINDINGS: The strategy with gefitinib or erlotinib first-line therapy and second-line gene-guided osimertinib therapy (GE-T790M) resulted in a gain of 0.31 quality-adjusted life year (QALY) at a cost of $15,200.95 per patient compared with the gefitinib or erlotinib first-line therapy and second-line chemotherapy (GE-chemotherapy). The incremental QALY and incremental cost values for first-line osimertinib therapy compared with GE-chemotherapy was 0.96 and $69,420.76, respectively. Compared with the GE-T790M strategy (0.96 QALY and $29,223.33), first-line osimertinib was estimated to be more effective (1.61 QALYs) and more costly ($83,443.14). Relative to the GE-chemotherapy strategy, the incremental cost-effectiveness ratios were $47,873.96 and $71,954.08 per QALY gained with GE-T790M and the osimertinib first-line strategy. The incremental cost-effectiveness ratio for first-line osimertinib versus GE-T790M was estimated to be $83,766.61. The results were found to be robust for univariate and multivariable sensitivity analyses. IMPLICATIONS: Gefitinib or erlotinib first-line and chemotherapy second-line strategies were the most cost-effective first-line treatments for EGFR mutations in patients with NSCLC. Gefitinib or erlotinib first-line and gene-guided osimertinib second-line strategies were more cost-effective than osimertinib first-line treatment for patients who preferred osimertinib administration in China.

Economic analysis of osimertinib in previously untreated EGFR-mutant advanced non-small cell lung cancer in Canada.

INTRODUCTION: Osimertinib improves progression-free survival in previously untreated EGFR-positive advanced non-small cell lung cancer (NSCLC) patients, with marked intracranial response rates. However, its cost-effectiveness in a publically funded health care system has not been established. We assessed the cost-effectiveness of first-line osimertinib from the public payer perspective in the Canadian health care system. METHODS: A Markov model was developed to project the outcomes and direct medical costs of initial treatment with osimertinib or current standard-of-care (SoC) EGFR TKIs, gefinitib or afatinib, in patients with previously untreated EGFR-mutant advanced NSCLC. Clinical and cost input estimates were informed from the available literature. Model outcomes included costs (in 2018 Canadian dollars), life years (LYs), quality-adjusted life-years (QALYs), and the cost utility of osimertinib compared to SoC EGFR TKI, or incremental cost per QALY gained. RESULTS: Initial treatment with osimertinib was associated with a gain of 0.79 QALY [95% confidence interval (CI), 0.74 to 0.83] at an incremental cost of $176,394 CAD (95% CI, 176,383 to 176,405) vs. SoC EGFR TKI (incremental cost-effectiveness ratio [ICER]: $223,133/QALY gained; 95%CI, 198,144 to 252,805). Osimertinib had a 0% probability of being cost-effective at a willingness-to-pay threshold of $100,000 per QALY. Deterministic sensitivity analysis showed that the cost of osimertinib had the largest impact on ICER results. CONCLUSION: At the current marketed price, first-line osimertinib therapy in patients with advanced EGFR-mutant lung adenocarcinoma is not cost-effective in Canada. Reduction of osimertinib cost, for example by 25%, can significantly improve the cost-effectiveness profile.

Ponatinib for Treating Chronic Myeloid Leukaemia: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

As part of its single technology appraisal process, the National Institute for Health and Care Excellence (NICE) invited the company that manufactures ponatinib (Inclusig®; Incyte Corporation) to submit evidence for the clinical and cost effectiveness for previously treated chronic myeloid leukaemia (CML) and Philadelphia-chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL). This paper focusses on the three phases of CML: the chronic phase (CP), the accelerated phase (AP) and the blast crisis phase (BP). The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). This article presents the critical review of the company's submission by the ERG and the outcome of the NICE guidance. Clinical evidence for ponatinib was derived from a phase II, industry-sponsored, single-arm, open-label, multicentre, non-comparative study. Despite the limited evidence and potential for biases, this study demonstrated that ponatinib was likely to be an effective treatment (in terms of major cytogenetic response and major haematological response) with an acceptable safety profile for patients with CML. Given the absence of any head-to-head studies comparing ponatinib with other relevant comparators, the company undertook a matching-adjusted indirect comparison (MAIC) of ponatinib with bosutinib. The approach was only used for patients with CP-CML because comprehensive data were not available for the AP- or BP-CML groups to allow the matching technique to be used. Despite the uncertainty about the MAIC approach, ponatinib was considered likely to offer advantages over bosutinib in the third-line setting, particularly for complete cytogenetic response. The company developed two health economic models to assess the cost effectiveness of ponatinib for the treatment of patients in CP-CML or in advanced CML (AP- or BP-CML, which were modelled separately). The company did not adequately explore the uncertainty in the survivor functions. As a result, the ERG believed the uncertainty in the decision problem was underestimated. Exploratory analyses undertaken by the ERG produced the following results for ponatinib. In CP-CML, from £18,246 to £27,667 per quality-adjusted life-year (QALY) gained compared with best supportive care (BSC), from £19,680 to £37,381 per QALY gained compared with bosutinib and from £18,279 per QALY gained to dominated compared with allogeneic stem cell transplant (allo-SCT). In AP-CML, the cost per QALY gained for ponatinib ranged from £7123 to £17,625 compared with BSC, and from dominating to £61,896 per QALY gained compared with allo-SCT. In BP-CML, the cost effectiveness of ponatinib ranged from £5033 per QALY gained to dominated compared with allo-SCT, although it was likely to be at the more favourable end of this range, and dominant in all scenarios compared with BSC. The NICE appraisal committee concluded that ponatinib is a cost-effective use of NHS resources in the considered population, subject to the company providing the agreed discount in the Patient Access Scheme.