Cost-Effectiveness Analysis of Screening for KRAS and BRAF Mutations in Metastatic Colorectal Cancer

Behl, Ajay S.; Goddard, Katrina A.B.; Flottemesch, Thomas J.; Veenstra, David L.; Meenan, Richard T.; Lin, Jennifer S; Maciosek, Michael V.

doi:10.1093/jnci/djs433

Cited by 87 publications

(109 citation statements)

References 52 publications

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“…Of the remaining 29 titles, the full papers were screened, which led us to exclude another 24, leaving five references: one HTA report (from Ontario) 61 and four papers. [62][63][64][65] A summary of the included studies is provided in Table 13 with a quality checklist based on Drummond et al 66 provided in Table 14.…”

Section: Resultsmentioning

confidence: 99%

“…The review of economic analyses of different methods for KRAS mutation testing to decide between standard chemotherapy and cetuximab in combination with standard chemotherapy in adults with mCRC found four full papers [62][63][64][65] and one HTA report. 61 Based on all of these publications it can be said that, in general, although KRAS testing is obviously a more cost-effective option than administering cetuximab to all patients, the ICER of KRAS testing and treating only patients with KRAS wild-type tumours with cetuximab compared with treating all patients with standard chemotherapy alone seems rather high.…”

Section: Cost-effectivenessmentioning

confidence: 99%

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

Westwood

Asselt

Ramaekers

et al. 2014

Health Technology Assessment

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Cost-effectivenessmentioning

confidence: 99%

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

Westwood

Asselt

Ramaekers

et al. 2014

Health Technology Assessment

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“…Second, a more appropriate treatment selection helps avoiding useless toxicities and may studies published between 2000 and 2013 56 have both suggested. The evidence, however, remains controversial and extensively debated 57,58 . Although reasonable, if the addition of NRAS testing may increment the cost-effectiveness of the use of EGFR-I is currently unproven.…”

Section: All Authors Contributed To Conception and Design Manuscriptmentioning

confidence: 99%

The relevance of BRAF and extended RAS mutational analyses for metastatic colorectal cancer patients

Aprile¹,

Macerelli²,

De³

et al. 2013

OA Molecular Oncology

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“…According to a study screening for KRAS and BRAF mutations can reduce the cost of anti-EGFR treatment for metastatic CRC but with a very small reduction in overall survival (Behl et al 2012 ). Metastatic CRC patients whose tumors harbor mutations in KRAS (and to a lesser extent, in BRAF) are unlikely to respond to costly anti-EGFR therapies.…”

Section: Cost-benefi T Analysis Of Kras and Braf Screening In Crcmentioning

confidence: 99%

Textbook of Personalized Medicine

Jain¹

2015

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Cost-Effectiveness Analysis of Screening for KRAS and BRAF Mutations in Metastatic Colorectal Cancer

Abstract: Screening for KRAS and BFAF mutation improves the cost-effectiveness of anti-EGFR therapy, but the incremental cost effectiveness ratio remains above the generally accepted threshold for acceptable cost effectiveness ratio of $100 000/quality adjusted life year.

Cited by 87 publications

References 52 publications

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

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

The relevance of BRAF and extended RAS mutational analyses for metastatic colorectal cancer patients

Textbook of Personalized Medicine

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