scholarly journals KRAS mutation testing of tumours in adults with metastatic colorectal cancer: a systematic review and cost-effectiveness analysis

2014 ◽  
Vol 18 (62) ◽  
pp. 1-132 ◽  
Author(s):  
Marie Westwood ◽  
Thea van Asselt ◽  
Bram Ramaekers ◽  
Penny Whiting ◽  
Manuela Joore ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Systematic Review ◽  
Cost Effectiveness ◽  
Metastatic Colorectal Cancer ◽  
Online Survey ◽  
Cost Effective ◽  
Mutation Testing ◽  
Standard Chemotherapy ◽  
The Uk ◽  
Quality Adjusted Life

BackgroundBowel cancer is the third most common cancer in the UK. Most bowel cancers are initially treated with surgery, but around 17% spread to the liver. When this happens, sometimes the liver tumour can be treated surgically, or chemotherapy may be used to shrink the tumour to make surgery possible. Kirsten rat sarcoma viral oncogene (KRAS) mutations make some tumours less responsive to treatment with biological therapies such as cetuximab. There are a variety of tests available to detect these mutations. These vary in the specific mutations that they detect, the amount of mutation they detect, the amount of tumour cells needed, the time to give a result, the error rate and cost.ObjectivesTo compare the performance and cost-effectiveness ofKRASmutation tests in differentiating adults with metastatic colorectal cancer whose metastases are confined to the liver and are unresectable and who may benefit from first-line treatment with cetuximab in combination with standard chemotherapy from those who should receive standard chemotherapy alone.Data sourcesThirteen databases, including MEDLINE and EMBASE, research registers and conference proceedings were searched to January 2013. Additional data were obtained from an online survey of laboratories participating in the UK National External Quality Assurance Scheme pilot forKRASmutation testing.MethodsA systematic review of the evidence was carried out using standard methods. Randomised controlled trials were assessed for quality using the Cochrane risk of bias tool. Diagnostic accuracy studies were assessed using the QUADAS-2 tool. There were insufficient data for meta-analysis. For accuracy studies we calculated sensitivity and specificity together with 95% confidence intervals (CIs). Survival data were summarised as hazard ratios and tumour response data were summarised as relative risks, with 95% CIs. The health economic analysis considered the long-term costs and quality-adjusted life-years associated with different tests followed by treatment with standard chemotherapy or cetuximab plus standard chemotherapy. The analysis took a ‘no comparator’ approach, which implies that the cost-effectiveness of each strategy will be presented only compared with the next most cost-effective strategy. The de novo model consisted of a decision tree and Markov model.ResultsThe online survey indicated no differences between tests in batch size, turnaround time, number of failed samples or cost. The literature searches identified 7903 references, of which seven publications of five studies were included in the review. Two studies provided data on the accuracy ofKRASmutation testing for predicting response to treatment in patients treated with cetuximab plus standard chemotherapy. Four RCTs provided data on the clinical effectiveness of cetuximab plus standard chemotherapy compared with that of standard chemotherapy in patients withKRASwild-type tumours. There were no clear differences in the treatment effects reported by different studies, regardless of whichKRASmutation test was used to select patients. In the ‘linked evidence’ analysis the Therascreen®KRASRGQ PCR Kit (QIAGEN) was more expensive but also more effective than pyrosequencing or direct sequencing, with an incremental cost-effectiveness ratio of £17,019 per quality-adjusted life-year gained. In the ‘assumption of equal prognostic value’ analysis the total costs associated with the various testing strategies were similar.LimitationsThe results assume that the differences in outcomes between the trials were solely the result of the different mutation tests used to distinguish between patients; this assumption ignores other factors that might explain this variation.ConclusionsThere was no strong evidence that any oneKRASmutation test was more effective or cost-effective than any other test.Study registrationPROSPERO CRD42013003663.FundingThe National Institute for Health Research Health Technology Assessment programme.

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 ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cost Effectiveness ◽  
Growth Factor ◽  
Metastatic Colorectal Cancer ◽  
Growth Factor Receptor ◽  
Cost Effective ◽  
Quality Adjusted Life Year ◽  
Wild Type ◽  
First Line ◽  
Quality Adjusted Life

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.

scholarly journals Cost-effectiveness of TAS-102 plus bevacizumab versus TAS-102 monotherapy in patients with metastatic colorectal cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kiyoaki Sugiura ◽  
Yuki Seo ◽  
Takayuki Takahashi ◽  
Hideyuki Tokura ◽  
Yasuhiro Ito ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Health Care ◽  
Sensitivity Analysis ◽  
Cost Effectiveness ◽  
Combination Therapy ◽  
Metastatic Colorectal Cancer ◽  
Cost Effective ◽  
Model Parameters ◽  
Combination Regimen ◽  
The Cost

Abstract Background TAS-102 plus bevacizumab is an anticipated combination regimen for patients who have metastatic colorectal cancer. However, evidence supporting its use for this indication is limited. We compared the cost-effectiveness of TAS-102 plus bevacizumab combination therapy with TAS-102 monotherapy for patients with chemorefractory metastatic colorectal cancer. Method Markov decision modeling using treatment costs, disease-free survival, and overall survival was performed to examine the cost-effectiveness of TAS-102 plus bevacizumab combination therapy and TAS-102 monotherapy. The Japanese health care payer’s perspective was adopted. The outcomes were modeled on the basis of published literature. The incremental cost-effectiveness ratio (ICER) between the two treatment regimens was the primary outcome. Sensitivity analysis was performed and the effect of uncertainty on the model parameters were investigated. Results TAS-102 plus bevacizumab had an ICER of $21,534 per quality-adjusted life-year (QALY) gained compared with TAS-102 monotherapy. Sensitivity analysis demonstrated that TAS-102 monotherapy was more cost-effective than TAS-102 and bevacizumab combination therapy at a willingness-to-pay of under $50,000 per QALY gained. Conclusions TAS-102 and bevacizumab combination therapy is a cost-effective option for patients who have metastatic colorectal cancer in the Japanese health care system.

Dose-escalation strategy in refractory metastatic colorectal cancer: A change in terms of cost-effectiveness

2021 ◽  
pp. 107815522199254
Author(s):  
Jacopo Giuliani ◽  
Francesco Fiorica ◽  
Giovanni Ponturo ◽  
Maurizio Azzurro ◽  
Andrea Ruzzenente ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cost Effectiveness ◽  
Metastatic Colorectal Cancer ◽  
Dose Escalation ◽  
Lower Cost ◽  
Cost Effective ◽  
Phase Iii ◽  
Controlled Trials ◽  
Pivotal Phase ◽  
Randomized Controlled

The analysis was conducted to assess the pharmacological costs of regorafenib and trifluridine/tipiracil in the treatment of refractory metastatic colorectal cancer (mCRC). Pivotal phase III randomized controlled trials (RCTs) of regorafenib and trifluridine/tipiracil in the treatment of refractory mCRC were considered. We have also considered the ReDOS trial, in order to verify if the dose-escalation strategy (practice changing for regorafenib) could influences the results. Differences in OS (expressed in months) between the different arms were calculated and compared with the pharmacological costs (at the Pharmacy of our Hospital and expressed in euros (€)) needed to get one month of OS. Trifluridine/tipiracil resulted the less expensive, with 1167.50 €per month OS-gained. The ReDOS trial further reduce costs with 510.41 €per month OS-gained in favour of regorafenib with the escalation-dose strategy. Both regorafenib and trifluridine/tipiracil can be considered economically sustainable treatments for refractory mCRC, apparently with a lower cost of trifluridine/tipiracil. The adoption of a dose-escalation strategy (ReDOS trial) could reverse the situation making regorafenib more cost-effective than trifluridine/tipiracil.

scholarly journals Cost-effectiveness analysis of cetuximab combined with chemotherapy as a first-line treatment for patients with RAS wild-type metastatic colorectal cancer based on the TAILOR trial

BMJ Open ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. e030738 ◽  
Author(s):  
Huijuan Wang ◽  
Lingfei Huang ◽  
Peng Gao ◽  
Zhengyi Zhu ◽  
Weifeng Ye ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cost Effectiveness ◽  
Metastatic Colorectal Cancer ◽  
Survival Benefit ◽  
Cost Effective ◽  
Phase Iii ◽  
Line Treatment ◽  
Wild Type ◽  
First Line ◽  
First Line Treatment

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.

Bevacizumab in addition to chemotherapy first-line for right-side metastatic colorectal cancer: A cost-effectiveness analysis.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 777-777
Author(s):  
Gong Chen ◽  
Maobai Liu ◽  
Te Li ◽  
Bin Wu
Keyword(s):  
Colorectal Cancer ◽  
Cost Effectiveness ◽  
Metastatic Colorectal Cancer ◽  
Cost Effective ◽  
Sensitivity Analyses ◽  
First Line ◽  
Assistance Program ◽  
Scenario Analyses ◽  
Bevacizumab Treatment ◽  
The Impact

777 Background: To test the cost-effectiveness of bevacizumab treatment compared with cetuximab plus irinotecan, fluorouracil, and leucovorin (FOLFIRI) as first-line treatment for patients with right-side metastatic colorectal cancer (mCRC). Methods: A Markov model was developed to Chinese clinical practice. The model incorporated clinical and utility data from published literatures, resource utilization and unit prices based on local charge. The lifetime horizontal was used and sensitivity analyses were carried out to test the robustness of the model results. The impact of patient assistance program (PAP) was also evaluated in scenario analyses. Results: Baseline analysis showed that the addition of cetuximab gained additional 0.232 QALYs with more $60,371 relative to bevacizumab therapy, resulting in an ICER of $259,775 /QALY. When PAP was available, the incremental cost decreased to $24,161, which yielded an ICER of $60,371 /QALY, which indicated that the strategy was not cost-effective at a willingness-to-pay (WTP) threshold of 3 times the per capita GDP of China ($22,200/QALY). Sensitivity analyses found that the costs of bevacizumab was the most influential parameter. Conclusions: Bevacizumab treatment for right-side mCRC is not a cost-effective option in comparison with standard chemotherapy in Chinese context.

Cetuximab and bevacizumab in addition to chemotherapy first-line for left-side metastatic colorectal cancer: A cost-effectiveness analysis.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 732-732
Author(s):  
Yanqiao Zhang ◽  
Tongsen Zheng ◽  
Maobai Liu ◽  
Te Li ◽  
Bin Wu
Keyword(s):  
Colorectal Cancer ◽  
Cost Effectiveness ◽  
Metastatic Colorectal Cancer ◽  
Cost Effective ◽  
Sensitivity Analyses ◽  
First Line ◽  
Assistance Program ◽  
Scenario Analyses ◽  
Bevacizumab Treatment ◽  
The Impact

732 Background: To test the cost-effectiveness of cetuximab and bevacizumab treatment as first-line treatment for patients with left-side metastatic colorectal cancer (mCRC). Methods: A Markov model was developed to Chinese clinical practice. The model incorporated clinical and utility data from published literatures, resource utilization and unit prices based on local charge. The lifetime horizontal was used and sensitivity analyses were carried out to test the robustness of the model results. The impact of patient assistance program (PAP) was also evaluated in scenario analyses. Results: Baseline analysis showed that the addition of cetuximab gained additional 0.364 QALYs with more $39,450 relative to bevacizumab therapy, resulting in an ICER of $108,287 /QALY. When PAP was available, the incremental cost decreased to $2,464, which yielded an ICER of $6,764 /QALY, which indicated that the strategy might be very cost-effective at a willingness-to-pay (WTP) threshold of 3 times the per capita GDP of China ($22,200/QALY). Sensitivity analyses found that the costs of cetuximab and bevacizumab were the most influential parameters. Conclusions: When PAP was available in Chinese context, cetuximab treatment is likely to be cost-effective versus bevacizumab therapy for patients with left-side mCRC.

Economic evaluation of laparoscopic surgery for colorectal cancer

2007 ◽  
Vol 23 (4) ◽  
pp. 464-472 ◽  
Author(s):  
Robyn M. de Verteuil ◽  
Rodolfo A. Hernández ◽  
Luke Vale ◽  
Keyword(s):  
Colorectal Cancer ◽  
Systematic Review ◽  
Laparoscopic Surgery ◽  
Cost Effectiveness ◽  
Incremental Cost ◽  
Open Surgery ◽  
Disease Free Survival ◽  
Cost Effective ◽  
Economic Evaluations ◽  
Short Term

Objectives: The aim of this study was to assess the cost-effectiveness of laparoscopic surgery compared with open surgery for the treatment of colorectal cancer.Methods: A Markov model was developed to model cost-effectiveness over 25 years. Data on the clinical effectiveness of laparoscopic and open surgery for colorectal cancer were obtained from a systematic review of the literature. Data on costs came from a systematic review of economic evaluations and from published sources. The outcomes of the model were presented as the incremental cost per life-year gained and using cost-effectiveness acceptability curves to illustrate the likelihood that a treatment was cost-effective at various threshold values for society's willingness to pay for an additional life-year.Results: Laparoscopic surgery was on average £300 more costly and slightly less effective than open surgery and had a 30 percent chance of being cost-effective if society is willing to pay £30,000 for a life-year. One interpretation of the available data suggests equal survival and disease-free survival. Making this assumption, laparoscopic surgery had a greater chance of being considered cost-effective. Presenting the results as incremental cost per quality-adjusted life-year (QALY) made no difference to the results, as utility data were poor. Evidence suggests short-term benefits after laparoscopic repair. This benefit would have to be at least 0.01 of a QALY for laparoscopic surgery to be considered cost-effective.Conclusions: Laparoscopic surgery is likely to be associated with short-term quality of life benefits, similar long-term outcomes, and an additional £300 per patient. A judgment is required as to whether the short-term benefits are worth this extra cost.

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