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Cost-effectiveness analysis of trastuzumab emtansine (T-DM1) in human epidermal growth factor receptor 2 (HER2): positive advanced breast cancer

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Abstract

Purpose

The EMILIA trial demonstrated that trastuzumab emtansine (T-DM1) significantly increased the median profession-free and overall survival relative to combination therapy with lapatinib plus capecitabine (LC) in patients with HER2-positive advanced breast cancer (ABC) previously treated with trastuzumab and a taxane. We performed an economic analysis of T-DM1 as a second-line therapy compared to LC and monotherapy with capecitabine (C) from both perspectives of the US payer and society.

Methods

We developed four possible Markov models for ABC to compare the projected life-time costs and outcomes of T-DM1, LC, and C. Model transition probabilities were estimated from the EMILIA and EGF100151 clinical trials. Direct costs of the therapies, major adverse events, laboratory tests, and disease progression, indirect costs (productivity losses due to morbidity and mortality), and health utilities were obtained from published sources. The models used 3 % discount rate and reported in 2015 US dollars. Probabilistic sensitivity analysis and model averaging were used to account for model parametric and structural uncertainty.

Results

When incorporating both model parametric and structural uncertainty, the resulting incremental cost-effectiveness ratios (ICER) comparing T-DM1 to LC and T-DM1 to C were $183,828 per quality-adjusted life year (QALY) and $126,001/QALY from the societal perspective, respectively. From the payer’s perspective, the ICERs were $220,385/QALY (T-DM1 vs. LC) and $168,355/QALY (T-DM1 vs. C).

Conclusions

From both perspectives of the US payer and society, T-DM1 is not cost-effective when comparing to the LC combination therapy at a willingness-to-pay threshold of $150,000/QALY. T-DM1 might have a better chance to be cost-effective compared to capecitabine monotherapy from the US societal perspective.

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References

  1. DeSantis CE, Lin CC, Mariotto AB et al (2014) Cancer treatment and survivorship statistics. CA Cancer J Clin 64(4):252–271

    Article  PubMed  Google Scholar 

  2. Le QA, Hay JW (2009) Cost-effectiveness analysis of lapatinib in HER-2-positive advanced breast cancer. Cancer 115(3):489–498

    Article  PubMed  Google Scholar 

  3. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235(4785):177–182

    Article  CAS  PubMed  Google Scholar 

  4. National Comprehensive Cancer Network. Breast Cancer (Version 1.2016). www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed Dec 2015

  5. Giordano SH, Temin S, Kirshner JJ et al (2014) Systemic therapy for patients with advanced human epidermal growth factor receptor 2–positive breast cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol 32(19):2078–2099

    Article  CAS  PubMed  Google Scholar 

  6. Verma S, Miles D, Gianni L et al (2012) Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 367(19):1783–1791

    Article  CAS  PubMed  Google Scholar 

  7. Geyer CE, Forster J, Lindquist D et al (2006) Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 355(26):2733–2743

    Article  CAS  PubMed  Google Scholar 

  8. Cameron D, Casey M, Press M et al (2008) A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses. Breast Cancer Res Treat 112:533–543

    Article  CAS  PubMed  Google Scholar 

  9. Squires H, Stevenson M, Simpson E, Harvey R, Stevens J (2016) Trastuzumab emtansine for treating her2-positive, unresectable, locally advanced or metastatic breast cancer after treatment with trastuzumab and a taxane: An Evidence Review Group Perspective of a NICE Single Technology Appraisal. Pharmacoeconomics. doi: 10.1007/s40273-016-0386-z

  10. pCODR Expert Review Committee (pERC) Final Recommendation (2014) Trastuzumab emtansine for metastatic breast cancer (MBC). https://www.cadth.ca/sites/default/files/pcodr/pcodr-kadcyla-mbc-fn-rec.pdf. Accessed 16 June 2015

  11. The Pharmaceutical Benefits Advisory Committee (PBAC) (2014) Trastuzumab Emtansine. http://www.pbs.gov.au/industry/listing/elements/pbac-meetings/psd/2014-03/trastuzumab-psd-03-2014.pdf. Accessed 16 June 2015

  12. Le QA (2016) Structural uncertainty of Markov models for advanced breast cancer: a simulation study of lapatinib. Med Decis Mak 36(5):629–640

    Article  Google Scholar 

  13. Beck JR, Kassirer JP, Pauker SG (1982) A convenient approximation of life expectancy (the “DEALE”). I. Validation of the method. Am J Med 73(6):883–888

    Article  CAS  PubMed  Google Scholar 

  14. Beck JR, Pauker SG, Gottlieb JE, Klein K, Kassirer JP (1982) A convenient approximation of life expectancy (the “DEALE”). II. Use in medical decision-making. Am J Med 73(6):889–897

    Article  CAS  PubMed  Google Scholar 

  15. Beck RJ, Pauker SG (1983) The Markov process in medical prognosis. Med Decis Mak 3(4):419–458

    Article  CAS  Google Scholar 

  16. McDowell M, Fryar CD, Ogden CL, Flegal KM (2008) National Health Statistics Reports, number 10: anthropometric reference data for children and adults: United States, 2003–2006

  17. Bureau of Labor Statistics. Consumer price index (CPI). http://www.bls.gov/cpi/. Accessed Jan 9, 2016

  18. Wan Y, Gao X, Mehta S, Wang Z, Faria C, Schwartzberg L (2013) Indirect costs associated with metastatic breast cancer. J Med Econ 16(10):1169–1178

    Article  PubMed  Google Scholar 

  19. Lloyd A, Nafees B, Narewska J, Dewilde S, Watkins J (2006) Health state utilities for metastatic breast cancer. Br J Cancer 95(6):683–690

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Elkin EB, Weinstein MC, Kuntz KM et al (2004) HER-2 testing and trastuzumab therapy for metastatic breast cancer: a cost-effectiveness analysis. J Clin Oncol 22:854–863

    Article  PubMed  Google Scholar 

  21. Montero AJ, Avancha K, Gluck S, Lopes G (2012) A cost-benefit analysis of bevacizumab in combination with paclitaxel in the first-line treatment of patients with metastatic breast cancer. Breast Cancer Res Treat 132(2):747–751

    Article  PubMed  Google Scholar 

  22. Price MJ, Welton NJ, Briggs AH, Ades AE (2011) Model averaging in the presence of structural uncertainty about treatment effects: influence on treatment decision and expected value of information. Value Health 14:205–218

    Article  PubMed  Google Scholar 

  23. Drug topics red book 2015 (online version). Thompson Healthcare, Montvale

  24. Sorensen SV, Goh JW, Pan F et al (2012) Incidence-based cost of illness model for metastatic breast cancer in the U.S. Int J Tech Assess Health Care 28:12–21

    Article  Google Scholar 

  25. Elting LS, Cantor SB, Martin CG (2003) Cost of chemotherapy-induced thrombocytopenia among patients with lymphoma or solid tumor. Cancer 97(6):1541–1550

    Article  PubMed  Google Scholar 

  26. Elting LS, Shih YC (2004) The economic burden of supportive care of cancer patients. Support Care Cancer 12(4):219–226

    Article  PubMed  Google Scholar 

  27. Burke TA, Wisniewski T, Ernst FR (2011) Resource utilization and costs associated with chemotherapy-induced nausea and vomiting (CINV) following highly or moderately emetogenic chemotherapy administered in the US outpatient hospital setting. Support Care Cancer 19(1):131–140

    Article  PubMed  Google Scholar 

  28. Dranitsaris G, Maroun J, Shah A (2005) Estimating the cost of illness in colorectal cancer who were hospitalized for severe chemotherapy-induced diarrhea. Can J Gastroenterol 19(2):83–87

    Article  PubMed  Google Scholar 

  29. Dranitsaris G, Maroun J, Shah A (2005) Severe chemotherapy-induced diarrhea in patients with colorectal cancer: a cost of illness analysis. Support Care Cancer 13(5):318–324

    Article  PubMed  Google Scholar 

  30. Borovicka JH, Calahan C, Gandhi M et al (2011) Economic burden of dermatologic adverse events induced by molecularly targeted cancer agents. Arch Dermatol 147(12):1403–1409

    Article  PubMed  Google Scholar 

  31. Kruse GB, Amonkar MM, Smith G et al (2008) Analysis of costs associated with administration of intravenous single-drug therapies in metastatic breast cancer in a US population. J Manag Care Pharm 14(9):844–857

    PubMed  Google Scholar 

  32. McLachlan SA, Pintilie M, Tannock IF (1999) Third line chemotherapy in patients with metastatic breast cancer: an evaluation of quality of life and cost. Breast Cancer Res Treat 54(3):213–223

    Article  CAS  PubMed  Google Scholar 

  33. Bureau of Labor Statistics. May 2015 National Occupational Employment and Wage Estimates United States. http://www.bls.gov/oes/current/oes_nat.htm. Accessed Jan 9 2016

  34. Tolley K, Goad C, Yi Y, Maroudas P, Haiderali A, Thompson G (2013) Utility elicitation study in the UK general public for late-stage chronic lymphocytic leukaemia. Eur J Health Econ 14(5):749–759

    Article  PubMed  Google Scholar 

  35. Matza LS, Sapra SJ, Dillon JF (2015) Health state utilities associated with attributes of treatments for hepatitis C. Eur J Health Econ 16(9):1005–1018

    Article  PubMed  Google Scholar 

  36. The World Bank. http://www.data.worldbank.org/indicator/NY.GDP.PCAP.CD?end=2015&locations=US&start=1960&view=chart%29. Accessed 1 July 2016

  37. The World Health Organization (WHO)—cost effectivenes and strategic planning. http://www.who.int/choice/costs/CER_levels/en/. Accessed 1 July 2016

  38. Hirth RA, Chernew ME, Miller E et al (2000) Willingness to pay for a quality-adjusted life year: in search of a standard. Med Decis Mak 20:332–342

    Article  CAS  Google Scholar 

  39. Ubel PA, Hirth RA, Chernew ME et al (2003) What is the price of life and why doesn’t it increase at the rate of inflation? Arch Intern Med 163:1637–1641

    Article  PubMed  Google Scholar 

  40. Braithwaite RS, Meltzer DO, King JT et al (2008) What does the value of modern medicine say about the $50,000 per quality-adjusted life-year decision rule? Med Care 46:349–356

    Article  PubMed  Google Scholar 

  41. Neumann PJ, Cohen JT, Weinstein MC (2014) Updating cost-effectivness—The curious resilience of $50,000-per-QALY threshold. N Engl J Med 371:796–797

    Article  CAS  PubMed  Google Scholar 

  42. Jackson CH, Bojke L, Thompson SG, Claxton K, Sharples LD (2011) A framework for addressing structural uncertainty in decision models. Med Decis Mak 31(4):662–674

    Article  Google Scholar 

  43. Bilcke J, Beutels P, Brisson M, Jit M (2011) Accounting for methodological, structural, and parameter uncertainty in decision-analytic models: a practical guide. Med Decis Mak 31(4):675–692

    Article  Google Scholar 

  44. MirandaRomero P, Marín Gil R (2015) Trastuzumab emtansine in locally advanced or metastatic HER2 positive breast cancer; GENESIS-SEFH drug evaluation report. Farm Hosp 39(3):171–175

    Google Scholar 

  45. Dusetzina SB (2016) Drug pricing trends for orally administered anticancer medications reimbursed by commercial health plans, 2000–2014. JAMA Oncol. doi:10.1001/jamaoncol.2016.0648

    Google Scholar 

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Acknowledgements

There is no financial support provided by any source for this study. Primary findings of this study were presented in part at the Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, IL, June 2nd, 2015.

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Correspondence to Quang A. Le.

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QAL received consultation fee from Genentech in the past unrelated to the current study. The other authors have no conflict of interest to declare.

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Le, Q.A., Bae, Y.H. & Kang, J.H. Cost-effectiveness analysis of trastuzumab emtansine (T-DM1) in human epidermal growth factor receptor 2 (HER2): positive advanced breast cancer. Breast Cancer Res Treat 159, 565–573 (2016). https://doi.org/10.1007/s10549-016-3958-x

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