scholarly journals Cost-Effectiveness of Liposomal Cytarabine-Daunorubicin (CPX-351) Compared to Conventional Cytarabine-Daunorubicin Chemotherapy in Acute Myeloid Leukemia

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 113-113
Author(s):  
Jan Philipp Bewersdorf ◽  
George Goshua ◽  
Kishan K Patel ◽  
Rory M. Shallis ◽  
Nikolai Podoltsev ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cost Effectiveness ◽  
Research Funding ◽  
Cost Effective ◽  
Phase Iii ◽  
Sensitivity Analyses ◽  
Inpatient Setting ◽  
Consolidation Therapy ◽  
Phase Iii Trial ◽  
Support Research

Abstract Introduction: A randomized phase III trial demonstrated improved overall survival (OS) and event-free survival (EFS) for older patients diagnosed with therapy-related AML (t-AML) or AML with myelodysplasia-related changes (AML-MRC) treated with a liposomal formulation of daunorubicin-cytarabine (CPX-351) when compared with 7+3 induction and consolidation therapy, a previous standard of care. Based on those results, CPX-351 was approved in 2017 in the United States (US) for adults with newly diagnosed t-AML and AML-MRC irrespective of age. However, the health economic implications of CPX-351 from a US payer perspective are not well-characterized. Methods: We constructed a partitioned survival analysis based on the data from the original phase III trial (Lancet et al. JCO 2018) and subsequent updates (Lancet et al. Lancet Haematology 2021) and post-hoc analyses from the landmark trial (Villa et al. JME 2019). Newly diagnosed AML patients at a median age of 68 years entered the model with active AML and received either CPX-351 or 7+3 induction and consolidation therapy followed by allogeneic hematopoietic cell transplant (allo-HCT) for some patients. Parametric survival distributions were fitted using patient-level data recreated from the Kaplan-Meier curves and at-risk tables for EFS and OS for both study arms. Log-logistic distributions demonstrated the best fit and were chosen for this model. Frequency and setting (inpatient vs outpatient) of re-induction and consolidation therapy were used as outlined in the original study. Costs and practice patterns of salvage therapy, receipt of allo-HCT, supportive care, and incidence of complications were derived from the original trial or published literature (Table). If available, costs for the Medicare population rather than commercially insured patients were used. For the CPX-351 arm, the maximum new technology add-on payment granted by the Centers for Medicare & Medicaid Services for fiscal year 2020 was added to the costs of inpatient induction and consolidation therapy in the 7+3 arm. Costs were adjusted for inflation to 2020 US dollars using the personal consumption expenditure health index. Previously published utilities were used and measured in quality-adjusted life years (QALYs). Costs and utilities were discounted by 3% annually (range 3-5% in one-way sensitivity analysis) and modelled over a 10-year time horizon. Model outputs were used to calculate the incremental cost-effectiveness ratio (ICER) for CPX-351 over 7+3. A willingness-to-pay (WTP) threshold of $150,000/QALY gained was used to determine cost-effectiveness. One-way sensitivity analyses were performed with utility values varied with a 10% range and all other variables across a 50% range. In probabilistic sensitivity analyses using 10,000 Monte Carlo simulations, beta distributions were used to describe probabilities and utilities, while gamma distributions were used for costs. Results: CPX-351 and 7+3 were associated with lifetime costs of $371,482 and $256,415, respectively, for an incremental cost of $115,066 with CPX-351. CPX-351 resulted in an incremental gain of 0.49 QALYs compared to 7+3 (CPX-351: 1.11 QALYs vs 7+3: 0.62 QALYs) resulting in an ICER of $231,563/QALY gained in the base case analysis. In one-way sensitivity analyses our model was most sensitive to the probability of receiving allo-HCT in either arm (Figure). In threshold analyses, a reduction of the CPX-351 add-on charge in the inpatient setting by 70.4% (from $47,353 to $14,004) would lower the ICER below the WTP threshold of $150,000/QALY. Probabilistic sensitivity analysis yielded a median ICER of $222,894 (95% credible interval: $142,863 - $313,289) with 7+3 favored in 96.4% of 10,000 iterations at a WTP threshold of $150,000. Conclusion: Use of CPX-351 under the current pricing model is unlikely to be cost-effective for most older patients with t-AML/AML-MRC who resemble those enrolled in the clinical trial. A reduction by 70.4% for the CPX-351 add-on charge in the inpatient setting would be necessary to lower the ICER below the conventional WTP threshold of $150,000/QALY. Higher rates of allo-HCT and outpatient consolidation with CPX-351 did not lead to gains in clinical utility or cost reductions substantial enough to make CPX-351 cost-effective. The implications of a potential outpatient administration of CPX-351 induction on its cost-effectiveness require additional studies. Figure 1 Figure 1. Disclosures Shallis: Curis: Divested equity in a private or publicly-traded company in the past 24 months. Podoltsev: PharmaEssentia: Honoraria; Blueprint Medicines: Honoraria; Pfizer: Honoraria; Incyte: Honoraria; CTI BioPharma: Honoraria; Bristol-Myers Squib: Honoraria; Novartis: Honoraria; Celgene: Honoraria. Huntington: Bayer: Honoraria; Thyme Inc: Consultancy; Servier: Consultancy; Novartis: Consultancy; SeaGen: Consultancy; AstraZeneca: Consultancy, Honoraria; Genentech: Consultancy; TG Therapeutics: Research Funding; Flatiron Health Inc.: Consultancy; DTRM Biopharm: Research Funding; AbbVie: Consultancy; Pharmacyclics: Consultancy, Honoraria; Celgene: Consultancy, Research Funding. Zeidan: Astex: Research Funding; Amgen: Consultancy, Research Funding; Epizyme: Consultancy; BMS: Consultancy, Other: Clinical Trial Committees, Research Funding; Aprea: Consultancy, Research Funding; Cardiff Oncology: Consultancy, Other: Travel support, Research Funding; AstraZeneca: Consultancy; Janssen: Consultancy; Daiichi Sankyo: Consultancy; Jasper: Consultancy; Astellas: Consultancy; Genentech: Consultancy; Geron: Other: Clinical Trial Committees; Agios: Consultancy; Novartis: Consultancy, Other: Clinical Trial Committees, Travel support, Research Funding; BioCryst: Other: Clinical Trial Committees; Pfizer: Other: Travel support, Research Funding; Kura: Consultancy, Other: Clinical Trial Committees; Incyte: Consultancy, Research Funding; BeyondSpring: Consultancy; Gilead: Consultancy, Other: Clinical Trial Committees; Ionis: Consultancy; Loxo Oncology: Consultancy, Other: Clinical Trial Committees; ADC Therapeutics: Research Funding; Jazz: Consultancy; Boehringer Ingelheim: Consultancy, Research Funding; Acceleron: Consultancy, Research Funding; AbbVie: Consultancy, Other: Clinical Trial Committees, Research Funding.

scholarly journals Survival of Mantle Cell Lymphoma in the Era of Bruton Tyrosine Kinase Inhibitors: A Population-Based Analysis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 182-182
Author(s):  
Mengyang Di ◽  
Can Cui ◽  
Shalin K. Kothari ◽  
Amer M. Zeidan ◽  
Nikolai Podoltsev ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Research Funding ◽  
Age Groups ◽  
Population Based ◽  
Sensitivity Analyses ◽  
Mantle Cell ◽  
All Cause Mortality ◽  
Bruton Tyrosine Kinase ◽  
Support Research

Abstract Background: Despite advances in chemoimmunotherapy and stem cell transplantation, mantle cell lymphoma (MCL) has historically been difficult to treat. Patients with advanced age and high-risk features (e.g. blastoid/pleomorphic features, high MIPI score, complex karyotype, TP53 mutation) face particularly poor outcomes with standard chemoimmunotherapy. Ibrutinib, a Bruton tyrosine kinase inhibitor (BTKi), was approved for second-line use in MCL in 2013. Other BTKis - acalabrutinib and zanubrutinib were approved in 2017 and 2019, respectively. BTKi provides a well-tolerated chemotherapy-free option for these hard-to-treat subgroups, especially the older patients. In this population-based study, we evaluated survival outcomes prior to and after the approval of ibrutinib, and hypothesized that survival benefit observed early after approval would be greatest in older patients not typically candidates for consolidative transplantation in the first-line setting. Methods: Using the Surveillance, Epidemiology, and End Results database, we included all adult patients diagnosed with MCL in the years 2007-2018 and followed them to the end of 2018 or death, whichever came first. The pre-BTKi era was defined by year of diagnosis 2007-2011, and the BTKi era was between 2014 and 2018. The years 2012-2013 were considered as a "washout" period to allow practice change related to the approval of ibrutinib. As age plays an important role in treatment decisions, including whether to use consolidative transplantation, patients were divided based on age at diagnosis: <60, 60-69, 70-79, and ≥80 years. Outcomes of interest included all-cause mortality, and mortality from MCL (MFM). We applied multivariable Cox proportional hazards regression model for all-cause mortality, adjusting for age, sex, race, stage, and median household income at census level, and reported adjusted hazard ratio (HR) with 95% confidence interval (CI). We also conducted multivariable competing risk analyses for MFM, considering all other causes of death as the competing events, and reported subhazard ratio (sHR) with 95% CI. To eliminate potential confounding by duration of follow-up among patients diagnosed in different periods, we used only three-year follow-up data for primary analyses, and all available follow-up data for sensitivity analyses. Results: We identified 7,625 individuals diagnosed with MCL during our study period (3,424 and 4,201 diagnosed during 2007-2011 and 2014-2018, respectively). The majority were male (71%) and white (90%), with 49% of patients 70 years or older. The median follow-up was 9.2 and 2.4 years for patients diagnosed during 2007-2011 and 2014-2018, respectively. The 3-year all-cause mortality and 3-year MFM rates were 39.8% and 27.3%, respectively, in the overall population. Both the 3-year all-cause mortality and MFM increased as age increased. The 3-year all-cause mortality was lower in the BTKi era among all age groups, except patients <60 years old, and the 3-year MFM was lower in the BTKi era among all age groups. The numeric difference of 3-year outcomes was more substantial in patients aged 70-79 for both all-cause mortality (pre-BTKi era: 47.8%, BTKi era: 40.4%) and MFM (pre-BTKi era: 33.9%, BTKi era: 27.5%) (Table, Figure A and B). In the multivariable analyses, risk of death was significantly lower during the BTKi era in the 60-69 (HR:0.85, 95% CI: 0.72-1.00) and 70-79 (HR: 0.80, 95% CI: 0.70-0.92) age groups. MFM was also significantly lower during the BTKi era in these two age groups (60-69: sHR: 0.78, 95% CI: 0.64-0.94; 70-79: sHR: 0.76, 95% CI: 0.65-0.90, Table). The results were largely unchanged in sensitivity analyses (results not shown). Conclusion: In this large population-based cohort analysis of individuals diagnosed with MCL, overall and lymphoma-specific survival improved in the BTKi era. At a median follow up of 2.4 years in our BTKi cohort, significant survival benefits were observed in those older than 60 but less than 80 years of age, and the observed benefits were greatest in the 70-79 age group. Future real-world studies should examine the impact of novel agents on treatment patterns and outcomes of MCL over a longer follow up period. Figure 1 Figure 1. Disclosures Kothari: Incyte pharmaceuticals: Consultancy, Honoraria; Karyopharm pharmaceuticals: Consultancy, Honoraria. Zeidan: Amgen: Consultancy, Research Funding; Astellas: Consultancy; Jasper: Consultancy; BMS: Consultancy, Other: Clinical Trial Committees, Research Funding; Boehringer Ingelheim: Consultancy, Research Funding; BeyondSpring: Consultancy; Acceleron: Consultancy, Research Funding; BioCryst: Other: Clinical Trial Committees; Novartis: Consultancy, Other: Clinical Trial Committees, Travel support, Research Funding; AbbVie: Consultancy, Other: Clinical Trial Committees, Research Funding; Ionis: Consultancy; Loxo Oncology: Consultancy, Other: Clinical Trial Committees; Astex: Research Funding; AstraZeneca: Consultancy; Epizyme: Consultancy; Cardiff Oncology: Consultancy, Other: Travel support, Research Funding; Janssen: Consultancy; Agios: Consultancy; ADC Therapeutics: Research Funding; Jazz: Consultancy; Genentech: Consultancy; Gilead: Consultancy, Other: Clinical Trial Committees; Incyte: Consultancy, Research Funding; Geron: Other: Clinical Trial Committees; Pfizer: Other: Travel support, Research Funding; Daiichi Sankyo: Consultancy; Kura: Consultancy, Other: Clinical Trial Committees; Aprea: Consultancy, Research Funding. Podoltsev: PharmaEssentia: Honoraria; Incyte: Honoraria; Novartis: Honoraria; Bristol-Myers Squib: Honoraria; CTI BioPharma: Honoraria; Celgene: Honoraria; Blueprint Medicines: Honoraria; Pfizer: Honoraria. Neparidze: Janssen: Research Funding; Eidos Therapeutics: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Research Funding. Shallis: Curis: Divested equity in a private or publicly-traded company in the past 24 months. Ma: Celgene/Bristol Myers Squibb: Consultancy, Research Funding. Huntington: AbbVie: Consultancy; TG Therapeutics: Research Funding; SeaGen: Consultancy; DTRM Biopharm: Research Funding; Flatiron Health Inc.: Consultancy; Novartis: Consultancy; Bayer: Honoraria; Pharmacyclics: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; Genentech: Consultancy; Servier: Consultancy; Thyme Inc: Consultancy; Celgene: Consultancy, Research Funding.

scholarly journals Cost Effectiveness Analysis of Venetoclax Plus Azacitidine Versus Azacitidine in Newly Diagnosed Adult Patients with Acute Myeloid Leukemia Who Are Ineligible for Intensive Chemotherapy from a United States Payer Perspective

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 112-112
Author(s):  
Keith W. Pratz ◽  
Xinglei Chai ◽  
Jipan Xie ◽  
Lei Yin ◽  
Xiaoyu Nie ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Research Funding ◽  
Time Horizon ◽  
Cost Effective ◽  
Sensitivity Analyses ◽  
Base Case ◽  
Intensive Chemotherapy ◽  
Publicly Traded ◽  
Analysis Group ◽  
Payer Perspective

Abstract Background: The phase 3 VIALE-A trial (NCT02993523) demonstrated that venetoclax plus azacitidine (VEN+AZA) improved overall survival (OS) and led to higher remission rates compared with AZA monotherapy, in patients with newly diagnosed (ND) acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy. Based on the results from VIALE-A, VEN+AZA received full United States (US) Food and Drug Administration approval in October 2020 for patients with ND AML aged ≥75 years, or who were ineligible for intensive induction chemotherapy due to comorbidities. This study aims to assess the long-term cost-effectiveness value of the VEN+AZA regimen from the VIALE-A trial from a US third-party payer perspective. Methods: A partitioned survival model with a 28-day cycle was developed to estimate costs and outcomes of treatment with VEN+AZA vs. AZA among patients with ND AML, who are ineligible for intensive chemotherapy, over a lifetime time horizon. The model included three health states: event-free survival (EFS), progressive/relapsed disease, and death. Within the EFS state, patients were further partitioned into time spent in complete remission (CR) or CR with incomplete marrow recovery (CRi), and time spent in non-CR/CRi. Efficacy inputs (OS, EFS, and CR/CRi rate) for both treatment arms were estimated using VIALE-A data. Best-fit parametric models per Akaike information criterion (AIC) were used to extrapolate OS until it reached EFS, and extrapolate EFS for each treatment until Year 5. Patients who remained in EFS after Year 5 were considered cured, and were assumed to have the same mortality as the US general population. Mean time on treatment (ToT) for both regimens was based on the time observed in VIALE-A. The costs for drug acquisition, drug administration for initial and subsequent treatments, subsequent stem cell transplant procedures, adverse events (AEs), and healthcare resource utilization (HRU) associated with each health state were obtained from the literature or publicly available data. All costs were inflated to 2021 US dollars. Utilities for each health state were estimated using EuroQol-5 dimension-5 level (EQ-5D-5L) data from VIALE-A, based on the US crosswalk value set. Information on disutilities due to Grade 3/4 AEs were obtained from the literature. Incremental cost-effectiveness ratios (ICERs) per life year (LY) and quality-adjusted life year (QALY) gained were estimated. Deterministic sensitivity analyses (DSA), scenario analyses and probabilistic sensitivity analyses (PSA) were performed to assess the robustness of the results. Results: Over a lifetime time horizon, compared with AZA, VEN+AZA was associated with an increase of 1.89 LYs (1.10 vs. 2.99, respectively) and 1.45 QALYs (0.84 vs. 2.30, respectively). Patients in the VEN+AZA arm incurred higher total costs ($250,486 vs. $110,034 for patients in the AZA arm). The ICER for VEN+AZA vs. AZA was estimated to be $74,141 per LY gained, and $96,579 per QALY gained. Results from the DSA and scenario analyses supported the base-case findings, with ICERs ranging from $60,922 to $138,554 per QALY gained. The results were most sensitive to alternative approaches for ToT estimation, subsequent treatment HRU costs, cure time point, and the extrapolation approach for EFS. Results from PSA showed that compared with AZA, VEN+AZA was cost-effective in 99.9% of cases at a willingness-to-pay (WTP) threshold of $150,000. Conclusions: Compared with AZA monotherapy, VEN+AZA results in a favorable ICER of $96,579 per QALY gained over a lifetime time horizon. The base-case results suggest that, compared with AZA, VEN+AZA is a cost-effective strategy based on a WTP threshold of $150,000 per QALY gained. Sensitivity analyses support the base-case results. Thus, VEN+AZA offers a cost-effective strategy in the treatment of patients with ND AML who are ineligible for intensive chemotherapy from a US third-party payer perspective. Disclosures Pratz: Agios: Consultancy; Abbvie: Consultancy, Honoraria, Research Funding; University of Pennsylvania: Current Employment; BMS: Consultancy, Honoraria; Novartis: Consultancy; Astellas: Consultancy, Honoraria, Research Funding; Cellgene: Consultancy, Honoraria; Millenium: Research Funding. Chai: Analysis Group, Inc.: Consultancy, Current Employment; Genentech, Inc.: Consultancy. Yin: Analysis Group, Inc.: Consultancy, Current Employment; Genentech, Inc.: Consultancy. Nie: Analysis Group, Inc.: Consultancy, Current Employment; Genentech, Inc.: Consultancy. Montez: Genentech, Inc: Current Employment, Other: May hold equity. Iantuono: Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months. Downs: Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Ma: Genentech, Inc.: Current Employment, Other: May hold equity.

scholarly journals Quality of Life and Cost-Effectiveness Assessment of Radioiodine Ablation Strategies in Patients With Thyroid Cancer: Results From the Randomized Phase III ESTIMABL Trial

2015 ◽  
Vol 33 (26) ◽  
pp. 2885-2892 ◽  
Author(s):  
Isabelle Borget ◽  
Julia Bonastre ◽  
Bogdan Catargi ◽  
Désirée Déandréis ◽  
Slimane Zerdoud ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Thyroid Cancer ◽  
Cost Effectiveness ◽  
Short Form ◽  
Cost Effective ◽  
Phase Iii ◽  
Sensitivity Analyses ◽  
Life Years ◽  
Tsh Stimulation

Purpose In the ESTIMABL phase III trial, the thyroid ablation rate was equivalent for the two thyroid-stimulating hormone (TSH) stimulation methods (thyroid hormone withdrawal [THW] and recombinant human TSH [rhTSH]) and the two iodine-131 (131I) activities (1.1 or 3.7 GBq). The objectives of this article were to present health-related quality-of-life (HRQoL) results and a cost-effectiveness evaluation performed alongside this trial. Patients and Methods HRQoL and utility were longitudinally assessed, from random assignment to the follow-up visit at 8 ± 2 months for the 752 patients with thyroid cancer, using the Short Form-36 and the EuroQoL-5D questionnaires, respectively. A cost-effectiveness analysis was performed from the societal perspective in the French context. Resource use (hospitalization for 131I administration, rhTSH, sick leaves, and transportation) was collected prospectively. We used the net monetary benefit approach and computed cost-effectiveness acceptability curves for both TSH stimulation methods and 131I activities. Sensitivity analyses of the costs of rhTSH were performed. Results At 131I administration, THW caused a clinically significant deterioration of HRQoL, whereas HRQoL remained stable with rhTSH. This deterioration was transient with no difference 3 months later. rhTSH was more effective than THW in terms of quality-adjusted life-years (QALYs; +0.013 QALY/patient) but more expensive (+€474/patient). The probability that rhTSH would be cost effective at a €50,000/QALY threshold was 47% in France. The use of 1.1 GBq of 131I instead of 3.7 GBq reduced per-patient costs by €955 (US$1,018) but with slightly decreased efficacy (−0.007 QALY/patient). Conclusion rhTSH avoids the transient THW-induced deterioration of HRQoL but is unlikely to be cost effective at its current price.

scholarly journals What Is the Cost-Effectiveness of Obinutuzumab Plus Bendamustine Followed By Obinutuzumab Monotherapy for the Treatment of Follicular Lymphoma Patients Who Relapse after or Are Refractory to a Rituximab-Containing Regimen in the US?

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3605-3605 ◽  
Author(s):  
Gregory F. Guzauskas ◽  
Anthony Masaquel ◽  
Carolina Reyes ◽  
Kenneth Wilhelm ◽  
Tania Krivasi ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Follicular Lymphoma ◽  
Patient Population ◽  
Cost Effective ◽  
Phase Iii ◽  
Sensitivity Analyses ◽  
Total Cost ◽  
The Us ◽  
Equity Ownership ◽  
The Cost

Abstract Background. Obinutuzumab (G) was recently approved for the treatment of follicular lymphoma (FL) in patients who relapsed after or are refractory to a rituximab (R)-containing regimen. In the phase III open label GADOLIN study of patients with rituximab-refractory iNHL, patients received either bendamustine (B, 120 mg/m2, d1+2, c1-6) alone, or obinutuzumab (G 1000 mg (d1, 8, 15 c1, d1 c2-6) for up to six 28d cycles) plus B (90 mg/m2, d1+2, c1-6) followed by G monotherapy (100 mg every 2 mo for up to 2 years). The net clinical benefit and economic value of G+B vs. B in R-refractory patients and the larger relapse patient population have not been formally evaluated. The objective of this study was to estimate the cost-effectiveness of G plus B followed by G monotherapy vs. B monotherapy based on results of the phase III GADOLIN trial in rituximab-refractory FL patients as well as model results for a refractory/relapse population. Methods. We developed a Markov model that utilized the GADOLIN trial's progression-free (PFS), and pooled G+B and B post-progression survival (PPS) through 4.5 years to model long-term patient PFS, progression, and death. We fit parametric curves to trial PFS and PPS data; PPS was used in lieu of immature overall survival (OS) data to model transitions to death from the progressed state. We used a U.S. registry of FL patients to inform the PFS and OS curves beyond the trial follow-up time to reflect a refractory/relapse patient population. The National LymphoCare Study is a disease-specific, prospective registry that enrolled more than 2,700 patients with newly diagnosed FL from 2004 to 2007 from more than 200 practice sites in the U.S. Drug utilization and adverse events were based on trial data, and costs were based on Medicare reimbursements and drug wholesale acquisition costs in 2016. Utility estimates were derived from the literature. Sensitivity analyses were conducted to assess uncertainty in the results. Results. Treatment with G+B followed by G monotherapy led to an increase in quality-adjusted life years (QALYs) relative to B-mono (1.23, 95% CR: -0.01, 2.38). The total cost of G+B was $114,815 and B-mono was $62,034, resulting in an incremental cost of $52,781. The average total cost was greater for G+B due primarily to increased drug and administration costs ($106,053 for G+B vs. $50,104 for B-mono), however this was offset by cost-savings for disease progression of -$4268 ($5,558 for G+B vs. $9,826 for B-mono). Adverse event costs were higher for G+B ($3,204) vs. B-mono ($2,103). The incremental cost-effectiveness ratio was $43,000 per QALY gained. In probabilistic sensitivity analyses, there was a 89% probability that G+B followed by G monotherapy was cost-effective versus B-mono at the $100,000 per QALY threshold. Conclusions. Our US-based analysis suggests that treatment with G+B followed by G monotherapy compared to B-mono is cost-effective in patients with FL who relapsed/refractory to a rituximab containing regimen. These findings are driven by the improvement in PFS with G+B treatment that lead to a projected increase in survival and decreased cost of treating disease progression. There was a high probability G+B was cost effective even when all parameters in the model were varied. In conclusion, G+B vs. B monotherapy in follicular lymphoma patients who relapse after or are refractory to a R-containing regimen is very likely cost effective in the US. Disclosures Guzauskas: Genentech, Inc.: Consultancy. Masaquel:Roche: Equity Ownership; Genentech: Employment. Reyes:Genentech: Employment; Roche: Equity Ownership. Wilhelm:Genentech: Employment; Roche: Equity Ownership. Krivasi:F. Hoffman-La Roche Ltd.: Employment. Veenstra:Genentech, Inc.: Consultancy.

scholarly journals Predicting Induction Toxicity with 7+3: Analysis of SWOG Trial S1203

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1403-1403 ◽  
Author(s):  
Megan Othus ◽  
Guillermo Garcia-Manero ◽  
Frederick R. Appelbaum ◽  
Harry P. Erba ◽  
Roland B. Walter
Keyword(s):  
Clinical Trial ◽  
Research Funding ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Cell Counts ◽  
Increased Risk ◽  
Multivariable Models ◽  
Grade 3 ◽  
Baseline Covariates ◽  
Support Research

Abstract Background: Prior work has shown that multivariable models can have reasonably high accuracy in predicting early deaths (deaths within 28 days of starting induction, defined as treatment-related mortality [TRM]) following intensive AML chemotherapy. These models can be used to derive a TRM score reflective of the probability of TRM with intensive AML therapy, and such scores can be used to make informed treatment decisions and as explicit eligibility criteria in AML protocols. The degree to which non-fatal toxicities can be predicted is unknown. It is also not known which patient characteristics are most strongly associated with occurrence of non-fatal toxicities following induction chemotherapy. Here, we examined these questions using data from the most recent SWOG Phase III with a 7+3 arm. Patients and Methods: We analyzed 260 eligible patients randomized to the 7+3 arm SWOG trial S1203 who received the first cycle of protocol therapy. 7+3 was per contemporary standard when the trial was opened in 2012: 100mg/m2 cytarabine on days 1-7 and 90mg/m2daunorubicin on days 1-3. Toxicities were reported using CTCAE version 4.0. We used logistic regression models to model toxicity incidence and evaluated the predictive accuracy of the models with the area under the receiver operating characteristic curve (AUC). We note that AUC of 0.5 is what would be expected with random chance or using a coin flip to make a decision, while an AUC of 1 denoted perfect prediction. We evaluated the following baseline covariates (modeled quantitatively unless otherwise specified): age at study registration, gender, Zubrod performance status (0-1 versus 2-3), pre-study white blood cell counts (WBC), pre-study platelets, pre-study marrow blasts, secondary vs. de novo AML, cytogenetic risk, and NPM1+ and FLT3-ITD- versus other NPM1/FLT3-ITD status. For toxicities with lower incidence, the number of covariates included in multivariable models was proportionate to one covariate per 10-15 patients with a toxicity. Toxicities were reported using the contemporary CTCAE version 4.0. Only toxicities observed during the first cycle of induction are analyzed below. Results: We evaluated the incidence grade 3 or higher thrombocytopenia (n=180, 70%), infection (n=166, 64%), anemia (n=159, 61%), neutropenia (n=145, 56%), lymphopenia (n=92, 35%), electrolyte abnormalities (n=66, 25%), liver abnormalities (n=37, 14%), cardiovascular abnormalities (n=20, 8%), constitutional symptoms (n=19, 7%), skin abnormalities (n=18, 7%), mucositis (n=17, 7%), GI tract abnormalities (n=16, 6%), pulmonary abnormalities (n=14, 5%), pain (n=13, 5%), endocrine abnormalities (n=12, 5%), bleeding (n=12, 5%), neurologic abnormalities (n=10, 4%), nausea/vomiting (n=7, 3%), kidney abnormalities (n=4, 2%). In univariate models no individual covariate was a strong predictor of toxicity. Only 3 pairs of toxicity/covariate had an AUC > 0.65 [indicating modest predictive ability]: older age predicting increased risk of endocrine abnormalities (OR=1.08 [per year], p=0.06, AUC=0.67), higher baseline WBC predicting increased risk for bleeding (OR=1.26 per 1,000, p=0.36, AUC=0.67), and higher baseline HGB predicting increased risk of neurologic toxicity (OR=1.33 per g/dL, p=0.10, AUC=0.69). As incidence allowed, we evaluate multivariable models. Multivariable models had increased AUC compared to univariate models, but no multivariable model had an AUC larger than 0.70. Conclusion: These findings indicate that with the baseline covariates evaluated, we have a poor ability to predict commonly occurring grade 3 and higher toxicities that occur during the first cycle of 7+3 induction therapy for AML. These findings support the claim that randomization is necessary to compare toxicities between standard and investigational regimens. Moreover, assuming that trial eligibility criteria are often stringent in an attempt to minimize the occurrence of treatment toxicities in study participants, the lack of strong association between individual baseline characteristics and toxicities could be used to argue for less-stringent study inclusion criteria. Support: NIH/NCI grants CA180888 and CA180819 Disclosures Walter: Aptevo Therapeutics, Inc: Consultancy, Other: Clinical Trial Support, Research Funding; Amphivena Therapeutics, Inc: Consultancy, Other: Clinical Trial Support, Research Funding; Covagen AG: Consultancy, Other: Clinical Trial Support, Research Funding; Seattle Genetics, Inc: Consultancy, Other: Clinical Trial Support, Research Funding; Pfizer, Inc: Consultancy; Amgen Inc: Other: Clinical Trial Support, Research Funding; Actinium Pharmaceuticals, Inc: Other: Clinical Trial support , Research Funding; Boehringer Ingelheim Pharma GmbH & Co. KG: Consultancy.

Cost-effectiveness of three years of adjuvant imatinib in gastrointestinal stromal tumors (GIST).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 137-137
Author(s):  
Myrlene Sanon ◽  
Anju Parthan ◽  
Douglas Taylor ◽  
John Coombs ◽  
Marc Paolantonio ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
Cost Effectiveness ◽  
Lifetime Cost ◽  
Cost Effective ◽  
Imatinib Therapy ◽  
Sensitivity Analyses ◽  
Adjuvant Imatinib ◽  
Lifetime Horizon ◽  
Life Years

137 Background: Recent clinical trial data have demonstrated that 3 years (yr) of adjuvant imatinib therapy for patients with surgically resected GIST leads to a significant improvement in recurrence free survival and overall survival vs. 1 yr of therapy. The objective of this study is to assess cost-effectiveness of treating with 3 yrs vs. 1 yr of adjuvant imatinib in the US from a payer’s perspective. Methods: A Markov model was developed to predict GIST recurrence, treatment (txt) costs, and quality-adjusted survival over a lifetime horizon. Patients transitioned between 3 health states: recurrence free GIST, GIST recurrence, and death. Monthly recurrence and mortality rates for 3 yr and 1 yr imatinib were derived from SSGXVIII/AIO clinical trial. The 5-yr recurrence rate observed in the trial was extrapolated for the remaining duration of the model horizon. First recurrence after active txt was treated with imatinib 400mg daily (800mg daily if recurrence during active txt). For subsequent disease progression, patients were treated with imatinib 800mg, sunitinib or best supportive care. After 5 years, txt specific mortality rate was applied for patients with recurrence. Costs and utilities were derived from published literature. Expected costs and quality-adjusted life years (QALYs) were estimated for each txt strategy. Costs and QALYs were discounted at 3% per yr. Extensive sensitivity analyses were conducted. Results: Total lifetime cost per patient was $302,100 with 3 yrs vs. $217,800 for 1 yr of imatinib therapy. Patients on 3 yrs of imatinib had higher QALYs (8.53 vs 7.18) vs. 1yr of imatinib. Incremental cost effectiveness ratio of 3 yrs of imatinib vs 1 yr of imatinib was $62,600/QALY. Model results were sensitive to rate of GIST recurrence beyond 5 yrs and monthly cost of adjuvant imatinib. At a threshold of $100,000/QALY, 3 yr imatinib therapy was cost-effective in 100% of simulations vs. 1 yr of imatinib. Conclusions: Model results suggest that treating patients with 3 yrs of imatinib is cost-effective vs. 1 yr of imatinib below the widely used $100,000/QALY threshold. Both clinical and economic results suggest treating surgically resected GIST patients with 3 yrs of imatinib would result in improved quality-adjusted and overall survival.

A cost-utility analysis of gemcitabine plus nab-paclitaxel in metastatic pancreatic cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e17569-e17569 ◽  
Author(s):  
Yoo-Joung Ko ◽  
Vincent Channing Tam ◽  
Nicole Mittmann ◽  
Mark Pasteka ◽  
Kelvin K. Chan
Keyword(s):  
Pancreatic Cancer ◽  
Cost Effectiveness ◽  
Cost Effective ◽  
The United States ◽  
Phase Iii ◽  
Sensitivity Analyses ◽  
Metastatic Pancreatic Cancer ◽  
Base Case ◽  
Public Healthcare ◽  
Term Care

e17569 Background: FOLFIRINOX has been shown to be superior to gemcitabine (gem) alone for metastatic pancreatic cancer (MPC) and has been established as the standard of care. A recent study (von Hoff et al, GI ASCO 2013) showed that gem + nab-paclitaxel (gem+nab-p) was superior to gem alone. The cost-effectiveness of gem+nab-p relative to gem or FOLFIRINOX has not been studied. Methods: A Markov cohort model was constructed for patients with MPC to examine the costs and outcomes of gem alone, gem+nab-p and FOLFIRINOX. Efficacy and side-effect data were obtained from pivotal phase III trials. Resource utilization data, unit costs and utilities were obtained from Ontario Ministry of Health and Long-Term Care, Sunnybrook Health Sciences Centre and the literature. The primary outcome was the incremental cost-effectiveness ratio (ICER) defined as cost per quality-adjusted life year (QALY). The analysis was conducted from the perspective of the Canadian public healthcare system over a 2-year time horizon adjusted to 2012 Canadian dollars (CAD$). Both cost and effectiveness were discounted at 5%. One way and probabilistic sensitivity analyses were performed. Results: Using gem as the base case, gem+nab-p had better outcomes but higher costs (see Table). The ICER was higher than conventional willingness-to-pay (WTP) threshold. Gem+nab-p was less effective but less costly when compared with FOLFIRINOX. It was dominated by combinations of gem and FOLFIRINOX (i.e. extended dominance), and therefore not cost-effective regardless of WTP threshold. If the price of nab-p was 20% lower, then gem+nab-p and FOLFORINOX would have similar cost-effectiveness. Conclusions: Gem+nab-p is not cost-effective, from the Canadian perspective, for the treatment of MPC based on the current price when compared with FOLFIRINOX. A lower-priced generic oxaliplatin, which is available in some jurisdictions including the United States, may affect the outcome of this analysis in further favor of FOLFIRINOX. [Table: see text]

Cost-effectiveness analysis of stereotactic ablative radiotherapy in patients with oligometastatic cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 7085-7085
Author(s):  
Abhishek Kumar ◽  
Christopher Andrew Straka ◽  
Lucas Vitzthum ◽  
Daniel R Cherry ◽  
Patrick T Courtney ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cost Effectiveness ◽  
Standard Therapy ◽  
Cost Effective ◽  
Sensitivity Analyses ◽  
Stereotactic Ablative Radiotherapy ◽  
Oligometastatic Disease ◽  
Cost Effective Treatment ◽  
The Cost ◽  
Oligometastatic Cancer

7085 Background: The SABR-COMET randomized clinical trial found that stereotactic ablative radiotherapy (SABR) improved outcomes among cancer patients with oligometastatic disease. Yet, the cost of SABR along with the large number of patients with oligometastatic disease raises the important question of value. This study sought to evaluate the cost-effectiveness of SABR compared to standard therapy among cancer patients with oligometastatic disease. Methods: We constructed a Markov model to simulate treatment with stereotactic ablative radiotherapy or standard therapy among patients with oligometastatic cancers. The model derived transition probabilities from clinical trial data to estimate risks of toxicity, disease progression and survival. Healthcare costs and health utilities were estimated from the literature. Cost-effectiveness was estimated with an incremental cost-effectiveness ratio (ICER) defined as dollars per quality-adjusted life year (QALY), with an ICER less than $100,000/QALY considered cost-effective. One-way and probabilistic sensitivity analyses were used to examine model uncertainty. Results: The addition of SABR increased total costs by $54,279 and improved effectiveness by 1.20 QALYs compared with standard therapy, leading to an ICER of $45,162/QALY. The model was sensitive to assumptions about tumor progression, though the model was not sensitive to assumptions about survival or cost of treatment. The cost of SABR would need to increase approximately six-fold from $12,241 to $78,151 before SABR becomes cost-ineffective. Probabilistic sensitivity analyses demonstrated that SABR was the cost-effective treatment option 97.2% of the time. Conclusions: The addition of SABR increased costs and improved quality adjusted survival, overall leading to a cost-effective treatment strategy for patients with oligometastatic cancer.

scholarly journals Cost-Effectiveness of Blinatumomab Versus Standard of Care in Adult Patients with Philadelphia-Chromosome-Negative B-Precursor Acute Lymphoblastic Leukemia in First Hematological Complete Remission (CR) with Minimal Residual Disease (MRD) from a US Payer Perspective

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4746-4746
Author(s):  
Thomas Delea ◽  
Nicholas Despiegel ◽  
Diana Boyko ◽  
Jordan Amdahl ◽  
Ze Cong ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
B Cell ◽  
Research Funding ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Cost Effective ◽  
Sensitivity Analyses ◽  
Cell Precursor ◽  
Payer Perspective ◽  
Life Years

Abstract INTRODUCTION: Blinatumomab is a bispecific CD19 directed CD3 T cell engager indicated for the treatment of adults and children with B-cell precursor acute lymphoblastic leukemia (ALL) in first or second complete remission (CR) with minimal residual disease (MRD) greater than or equal to 0.1%. In BLAST (NCT01207388), an open-label, multicenter, single-arm, phase 2 study of blinatumomab in patients with MRD positive B-precursor ALL in hematological CR, blinatumomab resulted in complete MRD response in cycle 1 in 78% of patients. Overall survival (OS) was significantly better in those with MRD vs those without MRD. The objective of this study is to evaluate the cost-effectiveness of blinatumomab vs. standard of care (SOC) therapy in patients with Ph- B-cell precursor ALL in first hematological CR with MRD based on the BLAST study from a US healthcare payer perspective. METHODS: A partitioned survival model was used to estimate the incremental cost-effectiveness ratio (ICER) of blinatumomab vs. SOC maintenance. A 50-year lifetime horizon and US payer perspective were employed. Costs and outcomes were discounted at 3% annually. Probabilities of complete MRD response, relapse-free survival (RFS), OS, numbers of cycles of blinatumomab and SOC, and transplant rates were estimated from BLAST and a historical cohort comparator study using propensity score analyses. RFS and OS were based on parametric survival distributions fit to individual patient failure-time data. Utility values were based from a generalized linear model/generalized estimating equation (GLM/GEE) model fitted to EQ-5D data collected in BLAST applying US tariffs. Inpatient and outpatient healthcare use by MRD status was from an observational study which evaluated treatment patterns and healthcare resource utilization in adult B-cell precursor ALL in first hematological CR with and without MRD. Deterministic and probabilistic sensitivity analyses were conducted to assess the effects of changes in model assumptions and uncertainty around key parameters. RESULTS: The unrestricted Gompertz distribution for RFS and lognormal mixture cure model distribution for OS were selected. In the base case, blinatumomab was projected to yield 3.52 additional life years and 2.93 additional quality-adjusted life years (QALYs) compared with SOC. Blinatumomab is associated with higher drug and administration costs and transplant costs, which were partially offset by lower post-relapse costs. The ICER for blinatumomab vs. SOC maintenance therapy was estimated to be $81,807/QALY gained (table). The main cost drivers were the drug acquisition costs and the additional hematopoietic stem cell transplant costs with blinatumomab. Cost-effectiveness was mostly sensitive to the uncertainty around the cure fraction (proportion of patients whose survival pattern is similar to the general cancer-free population) and transplant rates. Assumptions that most affected cost-effectiveness were the duration of benefit of blinatumomab and the long-term mortality estimation. The cost-effectiveness remained below the willingness-to-pay threshold value of $150,000/QALY gained in all scenarios tested. In the probabilistic sensitivity analyses, the estimated probability that blinatumomab is cost-effective was 87% at a willingness-to-pay threshold of $150,000/QALY. CONCLUSIONS: Blinatumomab is a cost effective treatment option vs. SOC for adults with Ph - B-precursor ALL in first hematological CR with MRD from the US healthcare perspective with an ICER well below the threshold of $150,000 per QALY gained. The value of blinatumomab is derived from its high complete MRD response rate, prolonged RFS, and OS. Disclosures Delea: Seattle Genetics: Research Funding; Takeda: Research Funding; Sanofi: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Policy Analysis Inc.: Employment. Despiegel:Amgen, Inc.: Employment, Equity Ownership. Boyko:Amgen: Research Funding. Amdahl:Amgen: Research Funding. Cong:Amgen, Inc.: Employment, Equity Ownership.

scholarly journals Cost-effectiveness analysis of ranibizumab for retinal vein occlusion patients in China from the societal perspective

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Weiyi Ni ◽  
Jia Liu ◽  
Yawen Jiang ◽  
Jing Wu
Keyword(s):  
Cost Effectiveness ◽  
Retinal Vein Occlusion ◽  
Societal Perspective ◽  
Laser Photocoagulation ◽  
Cost Effective ◽  
Sensitivity Analyses ◽  
Gdp Per Capita ◽  
Base Case ◽  
Vein Occlusion ◽  
Per Capita

Abstract Background Clinical trials in China have demonstrated that ranibizumab can improve the clinical outcomes of branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO). However, no economic evaluation of ranibizumab has been conducted among Chinese patient population. Methods To provide insights into the economic profile of ranibizumab among Chinese RVO population, a Markov state-transition model was used to predict the outcomes of ranibizumab comparing to laser photocoagulation and observational-only care from the societal perspective. This model simulated changes in patient visuality, quality-adjusted of life years (QALY), medical costs, and direct non-medical costs of individuals with visual impairment due to BRVO or CRVO in lifetime. The base-case analysis used an annual discount rate of 5% for costs and benefits following the China Guidelines for Pharmacoeconomic Evaluations. Deterministic and probabilistic sensitivity analyses were performed to test the robustness of the model. Results The base-case incremental cost-effectiveness ratio (ICER) comparing ranibizumab to laser photocoagulation was ¥65,008/QALY among BRVO patients and was ¥65,815/QALY among CRVO patients, respectively. Comparing to the 2019 gross domestic product (GDP) per capita of ¥71,000, both two ICERs were far below the cost-effective threshold at three times of GDP per capita (¥213,000). The deterministic and probabilistic sensitivity analyses demonstrated the base-case results were robust in most of the simulation scenarios. Conclusion The current Markov model demonstrated that ranibizumab may be cost-effective compared with laser photocoagulation to treat BRVO and cost-effective compared to observation-only care to treat CRVO in China from the societal perspective.

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