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PLoS One. 2016 Jan 22;11(1):e0146551. doi: 10.1371/journal.pone.0146551. eCollection 2016.

Comparative Cost-Effectiveness of Drugs in Early versus Late Stages of Cancer; Review of the Literature and a Case Study in Breast Cancer.

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Department of Pharmacy, Unit of PharmacoEpidemiology and PharmacoEconomics (PE2), University of Groningen, Groningen, The Netherlands.
University Medical Center Groningen (UMCG), Institute of Science in Healthy Aging & healthcaRE (SHARE), University of Groningen, Groningen, The Netherlands.



Many oncological drugs that are being used in the adjuvant setting were first submitted for reimbursement in the metastatic stage, with differences in incremental cost-effectiveness ratios (ICERs) in both settings having potential implications for reimbursement and pricing. The aim of this study is to identify a possible trend in the cost-effectiveness for the early/adjuvant and late/metastatic stages of oncological drugs through review and case study.


We reviewed pairs of cost-effectiveness analyses of the same oncological drug in different stages for Scotland and the Netherlands. The case study in this report was directed at trastuzumab in the Dutch situation. Using a simplified Markov model, the cost-effectiveness in early and late stage of breast cancer was calculated and compared to the findings from the review.


Comparable studies were found for cetuximab, bortezomib and bosutinib. Treatments in the late stage were found to be more expensive per QALY by a factor ranging from 1.5 to 12. The case study provided a similar result; late stage treatment was more expensive by a factor 10. Using, for example, a threshold of € 80,000/QALY, the early stage of cetuximab, bosutinib and trastuzumab are deemed cost-effective, while their compared late stage is lifted over the threshold and potentially considered not cost-effective.


ICERs of oncological drugs used in different stages are more unfavourable in the late stage than in the early stage. Applying a reasonable threshold may result in early stage treatment being deemed cost-effective while late stage potentially not. Authorities should be aware of this when assessing oncological drugs and interpreting the corresponding ICERs, in the situation where oncological drugs are generally most submitted for reimbursement in the late stage initially.

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