scholarly journals Cost-Effectiveness Analysis of Different Sequences of the Use of Epidermal Growth Factor Receptor Inhibitors for Wild-Type KRAS Unresectable Metastatic Colorectal Cancer

2016 ◽  
Vol 12 (6) ◽  
pp. e710-e723 ◽  
Author(s):  
Maria Carmen Riesco-Martínez ◽  
Scott R. Berry ◽  
Yoo-Joung Ko ◽  
Nicole Mittmann ◽  
Angie Giotis ◽  
...  

Purpose: Patients with unresectable wild-type KRAS metastatic colorectal cancer benefit from fluoropyrimidines (FP), oxaliplatin (O), irinotecan (I), bevacizumab (Bev), and epithelial growth factor receptor inhibitors (EGFRI). The most cost-effective regimen remains unclear. Methods: A Markov model was constructed to examine the costs and outcomes of three treatment strategies: strategy A (reference strategy): EGFRI monotherapy in third line ([3L]; ie, first-line [1L]: Bev + FOLFIRI [FP + I] or FOLFOX [FP + O]; second line [2L]: FOLFIRI/FOLFOX; 3L: EGFRI); strategy B: EGFRI and I in 3L (ie, 1L: Bev + FOLFIRI/FOLFOX; 2L: FOLFIRI/FOLFOX; 3L: EGFRI + I); and strategy C: EGFRI in 1L (ie, 1L: EGFRI + FOLFIRI/FOLFOX; 2L: Bev + FOLFIRI/FOLFOX; 3L: best supportive care). Efficacy data of the treatments were obtained from the literature. Health system resource use information was derived from chart review and the literature. Using Euro-QOL 5 Dimensions, utilities were obtained by surveying medical oncologists and costs from the Ontario Ministry of Health and the literature. The perspective of the Canadian public health care system was used over a 5-year time horizon with a 5% discount in 2012 Canadian dollars. Results: All three strategies had similar efficacy, but strategy C was most expensive. The incremental cost-effectiveness ratios (ICERs) for strategies B and C compared with A were 119,623 and 3,176,591, respectively. The model was primarily driven by the acquisition cost of the drugs. Strategy B was most cost effective when the willingness-to-pay threshold was > $130,000 per quality-adjusted life-year. Sensitivity analysis showed that strategy C would be cost-effective only when the progression-free survival of EGFRI is better than Bev in 1L with hazard ratio < 0.23 at willingness-to-pay of $150,000 per quality-adjusted life-year. Conclusion: First-line use of EGFRI in metastatic colorectal cancer is not cost effective at its current pricing relative to Bev.

2021 ◽  
Vol 11 ◽  
Author(s):  
Shing Fung Lee ◽  
Horace C. W. Choi ◽  
Sik Kwan Chan ◽  
Ka On Lam ◽  
Victor H. F. Lee ◽  
...  

ObjectivesWe aimed to compare the economic value of chemotherapy plus anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody (mAb) against chemotherapy with bevacizumab (Bev, an anti-vascular endothelial growth factor mAb) as first-line treatment in KRAS wild-type (WT), pan-RAS WT and pan-RAS WT left-sided metastatic colorectal cancer (mCRC) patients from the Hong Kong societal perspective.Materials and MethodsWe developed Markov models and 10-year horizon to estimate costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) of chemotherapy plus anti-EGFR therapy against chemotherapy plus Bev in KRAS WT, pan-RAS WT, and pan-RAS WT left-sided mCRC. We considered two times of the local gross domestic product per capita (GDPpc) as the willingness-to-pay (WTP) threshold (2× GDPpc; US$97,832).ResultsAdding anti-EGFR mAb to chemotherapy provides additional 0.24 (95% confidence interval [CI] 0.19–0.29), 0.32 (95% CI 0.27–0.37), and 0.57 (95% CI 0.49–0.63) QALY compared to adding Bev in KRAS WT, pan-RAS WT, and left-sided pan-RAS WT mCRC populations respectively. The corresponding ICER is US$106,847 (95% CI 87,806–134,523), US$88,565 (95% CI 75,678–105,871), US$76,537 (95% CI 67,794–87,917) per QALY gained, respectively.ConclusionsAnti-EGFR therapy is more cost-effective than Bev as a first-line targeted therapy in left-sided pan-RAS WT and pan-RAS WT, with ICER &lt;US$100,000/QALY, compared to KRAS WT mCRC population.


BMJ Open ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. e030738 ◽  
Author(s):  
Huijuan Wang ◽  
Lingfei Huang ◽  
Peng Gao ◽  
Zhengyi Zhu ◽  
Weifeng Ye ◽  
...  

ObjectivesCetuximab plus leucovorin, fluorouracil and oxaliplatin (FOLFOX-4) is superior to FOLFOX-4 alone as a first-line treatment for patients with metastatic colorectal cancer with RAS wild-type (RAS wt mCRC), with significantly improved survival benefit by TAILOR, an open-label, randomised, multicentre, phase III trial. Nevertheless, the cost-effectiveness of these two regimens remains uncertain. The following study aims to determine whether cetuximab combined with FOLFOX-4 is a cost-effective regimen for patients with specific RAS wt mCRC in China.DesignA cost-effectiveness model combined decision tree and Markov model was built to simulate pateints with RAS wt mCRC based on health states of dead, progressive and stable. The health outcomes from the TAILOR trial and utilities from published data were used respectively. Costs were calculated with reference to the Chinese societal perspective. The robustness of the results was evaluated by univariate and probabilistic sensitivity analyses.ParticipantsThe included patients were newly diagnosed Chinese patients with fully RAS wt mCRC.InterventionsFirst-line treatment with either cetuximab plus FOLFOX-4 or FOLFOX-4.Main outcome measuresThe primary outcomes are costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs).ResultsBaseline analysis disclosed that the QALYs was increased by 0.383 caused by additional cetuximab, while an increase of US$62 947 was observed in relation to FOLFOX-4 chemotherapy. The ICER was US$164 044 per QALY, which exceeded the willingness-to-pay threshold of US$28 106 per QALY.ConclusionsDespite the survival benefit, cetuximab combined with FOLFOX-4 is not a cost-effective treatment for the first-line regime of patients with RAS wt mCRC in China.Trial registration numberTAILOR trial (NCT01228734); Post-results.


2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 133-133
Author(s):  
Ilse Van Oostrum ◽  
Yannan Hu ◽  
Zijiao Yuan ◽  
Michael Schlichting ◽  
Libo Tao ◽  
...  

133 Background: Adding cetuximab to FOLFIRI chemotherapy (cet+CT) as first-line (1L) treatment for RAS wild-type (wt) metastatic colorectal cancer (mCRC) has been reported as cost-effective vs bevacizumab + FOLFIRI (bev+CT) in multiple jurisdictions. This study determined the cost-effectiveness (CE) of cet+CT for patients with mCRC in China. Methods: A published 3–health-state (nonprogressive, progressive, death) CE model was adapted to reflect Chinese patient characteristics, health state utilities, unit costs, and discounting rates, applying FIRE-3 trial–based resource utilization and adverse event rates. Progression-free and overall survival estimates were based on published FIRE-3 trial simulations to statistically adjust for available later-line treatment modalities in China vs those observed in FIRE-3. [1] Cetuximab and bevacizumab costs were based on up-to-date prices after the 2019 national reimbursement drug listing negotiations. Incremental CE ratios (ICERs) are given as cost (Chinese Yuan [¥]) per life-year (LY) and quality-adjusted LY (QALY) gained. The willingness-to-pay (WTP) threshold was ¥193,931, equivalent to 3 times the gross domestic product per capita, following WHO guidance. Results: Overall costs/costs restricted to 1L treatment were ¥483,771/¥249,619 (cet+CT) and ¥366,036/¥156,802 (bev+CT). Health effects were 3.32/2.68 (cet+CT) and 2.39/1.94 (bev+CT) LYs/QALYs gained. Discounted ICERs for cet+CT vs bev+CT were ¥148,311 and ¥186,517 per LY and QALY gained in deterministic analysis. cet+CT had a 71.8% (LY) and 52.5% (QALY) probability of being cost-effective. Treatment duration with a biologic in 1L, utilities in 3L treatment, and duration of 2L treatment were the main outcome drivers. Conclusions: Projections suggest that cet+CT is cost-effective vs bev+CT for 1L treatment of patients with RAS wt mCRC in China, with ICERs below the current WTP threshold in deterministic and probabilistic sensitivity analyses. [1] Van Oostrum I, et al. Value Health. 2020;23(Suppl 1): S8.


2019 ◽  
Vol 26 (5) ◽  
Author(s):  
W. W.L. Wong ◽  
M. Zargar ◽  
S. R. Berry ◽  
Y. J. Ko ◽  
M. Riesco-Martínez ◽  
...  

Background Evidence from a retrospective analysis of multiple large phase iii trials suggested that primary tumour location (ptl) in RAS wild-type metastatic colorectal cancer (wtRAS mcrc) might have predictive value with respect to response to drug therapies. Recent studies also show a potential preferential benefit for epidermal growth factor inhibitors (egfris) for left-sided tumours. In the present study, we aimed to determine the incremental costeffectiveness ratio (icer) for the first-line use of an egfri for patients with left-sided wtRAS mcrc.Methods We developed a state-transition model to determine the cost effectiveness of alternative treatmentstrategies in patients with left-sided mcrc:■ Standard of care■ Use of an egfri in first-line therapyThe cohort for the study consisted of patients diagnosed with unresectable wtRAS mcrc with an indication for chemotherapy and previously documented ptl. Model parameters were obtained from the published literature and calibration. The perspective was that of a provincial ministry of health in Canada. We used a 5-year time horizon and an annual discount rate of 1.5%.Results Selecting patients for first-line egfri treatment based on left-sided location of their colorectal primary tumour was more effective than the standard of care, resulting in an increase in quality-adjusted life-years (qalys) of 0.226 (or 0.644 life-years gained). However, the strategy was also more expensive, costing an average of $60,639 more per patient treated. The resulting icer was $268,094 per qaly. A 35% price reduction in the cost of egfri would be needed to make this strategy cost-effective at a willingness-to-pay threshold (wtp) of $100,000 per qaly.Conclusions Selective use of an egfri based on ptl was more cost-effective than unselected use of those agents; however, based on traditional wtp thresholds, it was still not cost-effective. While awaiting the elucidation of more precise predictive biomarkers that might improve cost-effectiveness, the price of egfris could be reduced to meet the wtp threshold.


ESMO Open ◽  
2018 ◽  
Vol 3 (3) ◽  
pp. e000315 ◽  
Author(s):  
Roberto Ivan López ◽  
Jenny Lissette Castro ◽  
Heidy Cedeño ◽  
Dagoberto Cisneros ◽  
Luis Corrales ◽  
...  

Colorectal cancer (CRC) is the third most common cancer in men and the second most common in women worldwide. In Latin America and the Caribbean, it has a mortality of 56%. The median overall survival for patients with metastatic colorectal cancer (mCRC) is currently estimated as ~30 months, which has substantially improved through strategic changes in treatment and in the management of patients. As opposed to other metastatic cancers where first-line regimens are often determined, mCRC requires special attention because there is controversy in the possible combinations of the available drugs and the different periods of duration for each patient. Each combination must seek to be effective and to generate the minimum adverse effects as possible. Instead of giving the first-line regimen until the tumour progresses, treatment is often individualised. Furthermore, up to 60% of colorectal tumours are considered non-mutated or wild-type CRC. Not harbouring mutations in the RAS family of genes or mutations in the signalling pathways of the epidermal growth factor receptor causes a null response to anti-epidermal growth factor receptor antibody therapy, which implies even more complex considerations regarding its management. The primary objective of this consensus is to address the main scenarios of mCRC in order to warrant the most appropriate therapeutic intervention for these patients in the Central American and the Caribbean (CAC) region. This can lead to better clinical outcomes as well as quality of life for palliative patients. This document includes the formal expert consensus recommendations for scenarios of mutated and non-mutated mCRC, including synchronous or metachronous disease, management of mCRC with liver and lung metastasis, resectable, potentially resectable or non-resectable tumours and local in the CAC context.


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