Cost-Effectiveness of First-Line Versus Second-Line Use of Daratumumab in Older, Transplant-Ineligible Patients With Multiple Myeloma

2021 ◽  
pp. JCO.20.01849
Author(s):  
Kishan K. Patel ◽  
Smith Giri ◽  
Terri L. Parker ◽  
Noffar Bar ◽  
Natalia Neparidze ◽  
...  

PURPOSE The MAIA trial found that addition of daratumumab to lenalidomide and dexamethasone (DRd) significantly prolonged progression-free survival in transplant-ineligible patients with newly diagnosed multiple myeloma, compared with lenalidomide and dexamethasone alone (Rd). However, daratumumab is a costly treatment and is administered indefinitely until disease progression. Therefore, it is unclear whether it is cost-effective to use daratumumab in the first-line setting compared with reserving its use until later lines of therapy. METHODS We created a Markov model to compare healthcare costs and clinical outcomes of transplant-ineligible patients treated with daratumumab in the first-line setting compared with a strategy of reserving daratumumab until the second-line. We estimated transition probabilities from randomized trials using parametric survival modeling. Lifetime direct healthcare costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated for first-line daratumumab versus second-line daratumumab from a US payer perspective. RESULTS First-line daratumumab was associated with an improvement of 0.52 QALYs and 0.66 discounted life-years compared with second-line daratumumab. While both treatment strategies were associated with considerable lifetime expenditures ($1,434,937 v $1,112,101 in US dollars), an incremental cost of $322,836 for first-line daratumumab led to an ICER of $618,018 per QALY. The cost of daratumumab would need to be decreased by 67% for first-line daratumumab to be cost-effective at a willingness-to-pay threshold of $150,000 per QALY. CONCLUSION Using daratumumab in the first-line setting for transplant-ineligible patients may not be cost-effective under current pricing. Delaying daratumumab until subsequent lines of therapy may be a reasonable strategy to limit healthcare costs without significantly compromising clinical outcomes. Mature overall survival data are necessary to more fully evaluate cost-effectiveness in this setting.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21104-e21104
Author(s):  
Nimer S. Alkhatib ◽  
Briana Choi ◽  
Hala Halawah ◽  
Matthias Calamia ◽  
Dexter Gulick ◽  
...  

e21104 Background: Crizotinib, alectinib, ceritinib, and brigatinib are approved as second line treatment for ALK+ NSCLC. Crizotinib was the first ALK inhibitor for first line therapy approved by Food and Drug Administration (2011) then ceritinib (2014), alectinib (2015), and brigatinib (2017) were approved as second line drugs. Following more data, these agents were approved as the first line therapy (2017 for ceritinib and alectinib; 2020 for brigatinib). These remain as a treatment option in patients who fail the first line therapy. Cost-effectiveness/utility analyses were conducted to assess clinical efficacy with varying costs of the agents. Methods: A three state Markov model were assumed (progression free, progression and death). Progression free survival (PFS) curves were digitized and fitted with exponential function. US payer perspective, a lifetime horizon, and discount rate of 3% were applied. Drug costs were Redbook wholesale acquisition cost. Other costs included were monitoring, adverse events and disease progression from published data (US$ 2020). Adverse events reported >5% in patients were included. Measured outcomes were PFS life years (PFSLY) and quality adjusted life years (PFSQALY). Crizotinib was the reference drug. Incremental cost-effectiveness and utility ratios (ICER/ICUR) of PFSLY and PFSQALY gained (PFSLYG, PFSQALYG) and lost were estimated. Base case (BCA) and probabilistic sensitivity analyses (PSA) were conducted. Results: Crizotinib was the reference drug for the following outcomes. For alectinib, with the decremental cost of -$14,653 (-$14,712), the incremental PFSLY of 0.16 (0.16) and PFSQALY of 0.05 (0.05) resulted in an ICER / PFSLYG of -$89,337 (-$88,604) and an ICUR / PFSQALYG of -$269,835 (-$266,510). For brigatinib, with the decremental cost of -$14,975 (-$14,954), the incremental PFSLY of 0.01 (0.01) and PFSQALY of ̃0.01 (0.02) yielded an ICER / PFSLYG of -$1,982,962 (-$1,431,631) and an ICUR / PFSQALYG of -$2,140,534 (-$570,538). For ceritinib, with the incremental cost of $7,590 ($7,514), there were decremental PFSLY of -0.01 (-0.01) and PFSQALY of -0.03 (-0.03). Conclusions: As second line treatment, crizotinib, ceritinib, and brigatinib had comparable PFSLYs and PFSQALYs while alectinib had the most PFSLY and PFSQALY and the lowest cost. Therefore, alectinib is the most cost-effective treatment for treating ALK+ NSCLC as the second line therapy.[Table: see text]


2015 ◽  
Vol 33 (10) ◽  
pp. 1112-1118 ◽  
Author(s):  
Daniel A. Goldstein ◽  
Qiushi Chen ◽  
Turgay Ayer ◽  
David H. Howard ◽  
Joseph Lipscomb ◽  
...  

Purpose The addition of bevacizumab to fluorouracil-based chemotherapy is a standard of care for previously untreated metastatic colorectal cancer. Continuation of bevacizumab beyond progression is an accepted standard of care based on a 1.4-month increase in median overall survival observed in a randomized trial. No United States–based cost-effectiveness modeling analyses are currently available addressing the use of bevacizumab in metastatic colorectal cancer. Our objective was to determine the cost effectiveness of bevacizumab in the first-line setting and when continued beyond progression from the perspective of US payers. Methods We developed two Markov models to compare the cost and effectiveness of fluorouracil, leucovorin, and oxaliplatin with or without bevacizumab in the first-line treatment and subsequent fluorouracil, leucovorin, and irinotecan with or without bevacizumab in the second-line treatment of metastatic colorectal cancer. Model robustness was addressed by univariable and probabilistic sensitivity analyses. Health outcomes were measured in life-years and quality-adjusted life-years (QALYs). Results Using bevacizumab in first-line therapy provided an additional 0.10 QALYs (0.14 life-years) at a cost of $59,361. The incremental cost-effectiveness ratio was $571,240 per QALY. Continuing bevacizumab beyond progression provided an additional 0.11 QALYs (0.16 life-years) at a cost of $39,209. The incremental cost-effectiveness ratio was $364,083 per QALY. In univariable sensitivity analyses, the variables with the greatest influence on the incremental cost-effectiveness ratio were bevacizumab cost, overall survival, and utility. Conclusion Bevacizumab provides minimal incremental benefit at high incremental cost per QALY in both the first- and second-line settings of metastatic colorectal cancer treatment.


2021 ◽  
Vol 12 ◽  
Author(s):  
Tan Chongqing ◽  
Li Sini ◽  
Zeng Xiaohui ◽  
Peng Liubao ◽  
Peng Ye ◽  
...  

Background: Pembrolizumab is a guideline-recommended, both first- and second-line treatment option for microsatellite-instability-high (MSI-H)/mismatch repair-deficient (dMMR)advanced colorectal cancer patients. The aim of the present study is to investigates the health and economic outcomes of three treatment strategies with or without pembrolizumab in MSI-H/dMMR advanced colorectal cancer to define the best treatment strategy from the perspective of the US payer.Methods: A microsimulation model was developed to estimate the cost and effectiveness of three treatment strategies: 1) pembrolizumab used as first-line, 2) pembrolizumab used as second-line and, 3) chemotherapy. Life years (LYs), quality-adjusted LYs (QALYs) and lifetime costs were estimated.Results: The model projected that patients receiving pembrolizumab in the first-line setting gained 5.579 QALYs; this value was 1.501 and 3.941 QALYs more than that for patients receiving pembrolizumab in the second-line setting and chemotherapy, respectively. First-line pembrolizumab strategy dominated second-line pembrolizumab strategy. Compared with chemotherapy, first-line pembrolizumab strategy yielded an incremental cost of $50613.7, which resulted in an ICER of $13441 per QALY.Conclusion: For patients with MSI-H/dMMR advanced colorectal cancer, reserving pembrolizumab for second-line line use is dominated by its first-line use, and first-line use of pembrolizumab is cost-effective compared with chemotherapy.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16010-e16010
Author(s):  
Yichen Zhong ◽  
Yizhen Lai ◽  
Haojie Li ◽  
Rachael Batteson ◽  
Yang Meng ◽  
...  

e16010 Background: Pembrolizumab is approved by the US Food and Drug Administration for the treatment of locally advanced or metastatic urothelial carcinoma (mUC) following platinum-based chemotherapy, based on results from KEYNOTE-045. In this randomized phase 3 trial, pembrolizumab significantly prolonged overall survival (OS) vs. chemotherapy in mUC patients (cut-off: Oct 26, 2017). The current analysis evaluates the cost-effectiveness of pembrolizumab vs. standard-of-care chemotherapy (docetaxel or paclitaxel) as second-line (2L) treatment for mUC, from a US payer perspective. Methods: We developed a partitioned-survival model to measure the costs and effectiveness over a 20-year time horizon to capture long-term costs and benefits from the treatments. Clinical efficacy, time on treatment, safety and utility data were derived from KEYNOTE-045. OS and progression-free survival were extrapolated beyond the trial period using piecewise models, i.e., Kaplan-Meier data followed by parametric function. Costs (in 2018 $US) for drug acquisition/administration, disease monitoring, adverse events management and terminal care were included. Costs and outcomes were discounted at 3% per year. Deterministic and probabilistic sensitivity analyses were conducted to assess the robustness of the results. Results: Pembrolizumab resulted in a mean gain of 1.33 life years (LYs) and 1.14 quality-adjusted life-years (QALYs) at an incremental cost of $103,861 vs. chemotherapy. The incremental cost-effectiveness ratios were $91,103/QALY and $78,254/LY. Key drivers of cost-effectiveness were extrapolation methods for OS data, time horizon and utility values. Pembrolizumab had a 72% or 100% probability of being cost-effective vs. chemotherapy at a $100,000 or $150,000 willingness-to-pay threshold, respectively. Conclusions: Pembrolizumab appears to be cost-effective vs. docetaxel or paclitaxel monotherapy as 2L mUC therapy when accounting for durable survival seen in a subset of patients receiving pembrolizumab. The model was established based on robust estimates, with key clinical endpoints directly drawn or derived from patient level data in KEYNOTE-045.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5031-5031
Author(s):  
Ali Raza Khaki ◽  
Leonidas Nikolaos Diamantopoulos ◽  
Marita Zimmerman ◽  
Louis P. Garrison ◽  
Petros Grivas

5031 Background: Data from interim analysis of IMvigor130 trial showed that 1st line treatment of advanced urothelial cancer (aUC) with atezolizumab (Atezo) + platinum-based chemotherapy (PBC) significantly improved progression-free survival (PFS), but not overall survival (OS), vs PBC. Switch maintenance anti-PD(L)1 after completion of PBC as 1st line therapy is an alternate strategy, recently reported to significantly prolong OS. We aimed to compare cost-effectiveness of combined treatment (Atezo+PBC) vs PBC based on IMvigor130. Methods: We used a partitioned-survival model to evaluate the potential cost-effectiveness of treatment with A) Atezo+PBC (gemcitabine with cisplatin or carboplatin) or B) PBC alone with checkpoint inhibitor pembrolizumab at progression (standard-of-care). PFS and OS curves were extracted from IMvigor 130 and parametric models were fit to approximate outcomes with Atezo+PBC with the hazard ratio (HR) from the trial used to project outcomes for PBC alone. We used a health-care payer perspective with a two-year time horizon. Model outputs — costs, life-years, quality-adjusted life years (QALYs) — were used to calculate an incremental cost-effectiveness ratio (ICER). A scenario analysis evaluated the “value-based price” needed for Atezo+PBC to be cost-effective; a one-way sensitivity analysis was also performed. Results: Results of the cost-effectiveness analysis are summarized in the table. The mean projected incremental cost of Atezo+PBC compared to PBC was $59,604 for a mean incremental gain of 0.09 life-years and 0.07 QALYs. This resulted in an ICER of $629,755/life-year and $895,800/QALY, respectively. A 33% reduction would be needed in the price of atezolizumab to make Atezo+PBC cost-effective at an ICER of $150,000/QALY. Results were sensitive to cost of pembrolizumab at progression, the cost of Atezo+PBC, and the OS HR between Atezo+PBC and PBC. Conclusions: Combined chemoimmunotherapy with atezolizumab and PBC would likely not be cost-effective for the first-line treatment of aUC. However, with a price rebate of 33%, it would approach being cost-effective at a widely used cost-effectiveness threshold. [Table: see text]


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18847-e18847
Author(s):  
Chia-Wei Lin ◽  
Katherine Rosettie ◽  
Pinar Bilir ◽  
Hazal Celik ◽  
Seye Abogunrin ◽  
...  

e18847 Background: Atezolizumab monotherapy is indicated as 1L treatment for mNSCLC patients with high programmed death ligand-1 (PD-L1) expression (≥ 50%) and without epidermal growth factor receptor or anaplastic lymphoma kinase mutations. This analysis assessed the cost-effectiveness of 1L atezolizumab monotherapy vs. pembrolizumab monotherapy for mNSCLC patients with high PD-L1 expression from a US third-party payer perspective. Methods: A Markov model with progression-free, progressive disease (PD), and death states was developed in Microsoft Excel to compare clinical and cost outcomes of atezolizumab monotherapy vs. pembrolizumab monotherapy. Efficacy, safety, and utility data were derived from systematic reviews and indirect comparisons of the IMpower110, Keynote-024, and Keynote-042 trials. Product prescribing information and clinical trials informed dosing and administration. Wholesale acquisition cost (WAC, accessed in January 2021) for drugs were used while other cost inputs were derived from publicly available fee schedules and peer-reviewed literature. The key outcome of interest was the incremental cost-effectiveness ratio (ICER) expressed as cost per quality-adjusted life-year (QALY) gained. Deterministic sensitivity analysis with 20% variation and probabilistic sensitivity analyses (PSA) were performed to address uncertainties around input parameters. Results: In the base case, 1L atezolizumab monotherapy was projected to increase life expectancy for patients by 0.60 life-years (4.35 vs. 3.75) and 0.47 QALYs (3.46 vs. 2.98) over pembrolizumab monotherapy at an incremental cost of $27,947 (mean total cost: $396,811 vs. $368,864), resulting in an ICER of $58,841/QALY gained. Results of the deterministic sensitivity analysis were most sensitive to changes in discount rates for costs and care costs in the PD state. The PSA showed that the probability of atezolizumab being cost-effective at willingness-to-pay thresholds of $100,000 and $150,000 was 41% and 49%, respectively. Conclusions: First-line atezolizumab monotherapy had 0.6 life-years and 0.47 QALYs gained compared with pembrolizumab monotherapy and was estimated to be cost-effective (ICER $58,841/QALY). As the ICER falls below the US cost-effectiveness thresholds ( < $100,000-$150,000/QALY), clinicians and payers should consider atezolizumab monotherapy as a cost-effective 1L option for mNSCLC patients with high PD-L1 expression.


Blood ◽  
2020 ◽  
Vol 136 (17) ◽  
pp. 1946-1955 ◽  
Author(s):  
Kishan K. Patel ◽  
Iris Isufi ◽  
Shalin Kothari ◽  
Amy J. Davidoff ◽  
Cary P. Gross ◽  
...  

Abstract The ALLIANCE A041202 trial found that continuously administered ibrutinib in the first-line setting significantly prolonged progression-free survival compared with a fixed-duration treatment of rituximab and bendamustine in older adults with chronic lymphocytic leukemia (CLL). In this study, we created a Markov model to assess the cost-effectiveness of ibrutinib in the first-line setting, compared with a strategy of using ibrutinib in the third-line after failure of time-limited bendamustine and venetoclax-based regimens. We estimated transition probabilities from randomized trials using parametric survival modeling. Lifetime direct health care costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated from a US payer perspective. First-line ibrutinib was associated with an improvement of 0.26 QALYs and 0.40 life-years compared with using ibrutinib in the third-line setting. However, using ibrutinib in the first-line led to significantly higher health care costs (incremental cost of $612 700), resulting in an ICER of $2 350 041 per QALY. The monthly cost of ibrutinib would need to be decreased by 72% for first-line ibrutinib therapy to be cost-effective at a willingness-to-pay threshold of $150 000 per QALY. In a scenario analysis where ibrutinib was used in the second-line in the delayed ibrutinib arm, first-line ibrutinib had an incremental cost of $478 823, an incremental effectiveness of 0.05 QALYs, and an ICER of $9 810 360 per QALY when compared with second-line use. These data suggest that first-line ibrutinib for unselected older adults with CLL is unlikely to be cost-effective under current pricing. Delaying ibrutinib for most patients with CLL until later lines of therapy may be a reasonable strategy to limit health care costs without compromising clinical outcomes.


Author(s):  
Tianfu Gao ◽  
Jia Liu ◽  
Jing Wu

Objective: To evaluate the cost-effectiveness of dabrafenib plus trametinib combination therapy versus vemurafenib as first-line treatment in patients with BRAF V600 mutation-positive unresectable or metastatic melanoma from a healthcare system perspective in China. Methods: This study employed a partitioned survival model with three health states (progression-free survival, post-progression survival and dead) to parameterize the data derived from Combi-v trial and extrapolated to 30 years. Health states’ utilities were measured by EQ-5D-3L, also sourced from the Combi-v trial. Costs including drug acquisition costs, disease management costs and adverse event costs were based on the Chinese Drug Bidding Database and physician survey in China. The primary outcomes of the model were lifetime costs, life-years (LYs), quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER). Deterministic and probabilistic sensitivity analyses were conducted, respectively. Result: Dabrafenib plus trametinib is projected to increase a patient’s life expectancy by 0.95 life-years over vemurafenib (3.03 vs. 2.08) and 1.09 QALY gains (2.48 vs. 1.39) with an incremental cost of $3833. The incremental cost-effectiveness ratio (ICER) was $3511 per QALY. In the probabilistic sensitivity analyses, at a threshold of $33,357 per QALY (three times the gross domestic product (GDP) per capita in China in 2020), the probability of dabrafenib plus trametinib being cost-effective was 90%. In the deterministic sensitivity analyses, the results were most sensitive to the dabrafenib plus trametinib drug costs, vemurafenib drug costs and discount rate of cost. Conclusion: Dabrafenib plus trametinib therapy yields more clinical benefits than vemurafenib. Using a threshold of $33,357 per QALY, dabrafenib plus trametinib is very cost-effective as compared with vemurafenib in China.


2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 199-199 ◽  
Author(s):  
Cheryl L. Attard ◽  
Stephen Brown ◽  
Karine Alloul ◽  
Malcolm J Moore

199 Background: The ACCORD 11/0402 trial demonstrates that FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) is significantly more efficacious than the current standard of gemcitabine (G) monotherapy in the first line treatment of metastatic pancreatic cancer (mPC). This study assesses for public payers the cost-effectiveness of first-line FOLFIRINOX compared to first-line G in Canadian mPC patients. Methods: A Markov model was used to estimate how patients progress through the following states: ‘stable’, ‘progressed’, ‘dead’. OS and PFS data were derived from the trial data. Published utility data and Canadian cost data were applied based on time in each state and treatment related adverse event (AE) rates. Costs included first and second-line therapy, monitoring, AE and end of life costs. Costs and outcomes are discounted at 5%. Two separate analyses were made. Analysis 1: Based on trial data (First-line FOLFIRINOX → second-line G versus First-line G → second-line platin-based chemo, G-CSF usage allowed). Analysis 2: Current Ontario Treatment Patterns (first-line FOLFIRINOX → second-line G vs first-line G → best supportive care, no G-CSF usage). Results: All analyses found that using first-line FOLFIRINOX produced more life years and QALY than treatment strategies that used first-line G. The probabilistic sensitivity analysis results for both analyses support the use of FOLFIRINOX for first-line treatment of mPC. FOLFIRINOX has a greater than 95% and 90% probability of being cost effective at an $80,000 threshold for Analysis 1 and Analysis 2 respectively. Conclusions: First-line FOLFIRINOX significantly prolongs median OS by more than 4 months over G (11.3 vs 6.8 months, HR=0.57). Given the favorable costs per QALYs, the improvement in clinical efficacy and the limited available treatment options, FOLFIRINOX represents an attractive cost-effective treatment for mPC. [Table: see text]


Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 931
Author(s):  
Chi-Leung Chiang ◽  
Sik-Kwan Chan ◽  
Shing-Fung Lee ◽  
Horace Cheuk-Wai Choi

Background: The IMbrave 150 trial revealed that atezolizumab plus bevacizumab (atezo–bev) improves survival in patients with unresectable hepatocellular carcinoma (HCC) (1 year survival rate: 67.2% vs. 54.6%). We assessed the cost-effectiveness of atezo–bev vs. sorafenib as first-line therapy in patients with unresectable HCC from the US payer perspective. Methods: Using data from the IMbrave 150, we developed a Markov model to compare the lifetime cost and efficacy of atezo–bev as first-line systemic therapy in HCC with those of sorafenib. The main outcomes were life-years, quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratio (ICER). Results: Atezo–bev demonstrated a gain of 0.44 QALYs, with an additional cost of USD 79,074. The ICER of atezo–bev was USD 179,729 per QALY when compared with sorafenib. The model was most sensitive to the overall survival hazard ratio and body weight. If we assumed that all patients at the end of the IMbrave 150 trial were cured of HCC, atezo–bev was cost-effective (ICER USD 53,854 per QALY). However, if all patients followed the Surveillance, Epidemiology, and End Results data, the ICER of atezo–bev was USD 385,857 per QALY. Reducing the price of atezo–bev by 20% and 29% would satisfy the USD 150,000/QALY and 100,000/QALY willingness-to-pay threshold. Moreover, capping the duration of therapy to ≤12 months or reducing the dosage of bev to ≤10 mg/kg would render atezo–bev cost-effective. Conclusions: The long-term effectiveness of atezo–bev is a critical but uncertain determinant of its cost-effectiveness. Price reduction would favorably influence cost-effectiveness, even if long-term clinical outcomes were modest. Further studies to optimize the duration and dosage of therapy are warranted.


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