Correspondence

Author: Alok A. Khorana MD1
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  • 1 Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, Ohio

The author responds: I welcome the opportunity to respond to the issues raised by Dr. Oo; I note that he has made similar critiques in other correspondence, to one of which I previously coauthored a response.1 Broadly speaking, Dr. Oo is opposed to outpatient thromboprophylaxis, with the exception of IMid-based regimens in patients with myeloma, because it has not been shown to improve survival, because prophylaxis may be expensive and because of concerns regarding extrapolation to larger populations from subgroup analysis. I would like to point out the obvious contradiction in this correspondence, because it is emblematic of the struggle around decision-making for outpatient thromboprophylaxis in general. The contradiction is in the exception: thromboprophylaxis for patients with myeloma receiving IMid-based regimens has not been shown to improve survival or to be cost-effective and the results have been extrapolated from larger randomized trials. Yet thousands of oncologists worldwide have no issues with routinely prescribing prophylaxis in this setting. Thus, it is clear that outpatient prophylaxis is acceptable if the clinical incidence is perceived to be high enough.

The stated objections to outpatient prophylaxis for select patients with solid tumors, therefore, do not cohere with the acceptance of prophylaxis in select patients with myeloma. However, the issues raised are important and worth clarifying. First, lack of survival benefit does not necessarily mean no additional benefits to patients with cancer. Indeed, in cancer supportive care, pharmacologic agents are widely used because reducing cancer-related complications is believed to be good for the patient in and of itself. Indeed, if we were to use survival as the only yardstick, antiemetics, opioids, and growth factors would have very limited use. Second, the statement that outpatient prophylaxis “will undoubtedly increase health care cost” would require a formal pharmacoeconomic analysis to prove. This is not a given because costs associated with cancer-associated VTE are quite substantial. In a recent analysis, we found that patients with cancer with VTE incurred higher overall all-cause inpatient costs (mean $21,299 vs $7459 per patient), outpatient costs ($53,660 vs $34,232 per patient), and total health care costs ($74,959 vs $41,691 per patient) than patients with cancer without VTE (all P<.0001).2

Finally, the concerns about subgroup analysis are worth considering. However, conflating these concerns with inpatient prophylaxis does not serve the argument. In the inpatient realm, there has not been a single cancer-specific clinical trial of prophylaxis, whereas there have been several large randomized trials in various populations comprising several thousand patients with cancer in the outpatient setting, with results largely demonstrating both safety and efficacy.3

The bottom line, therefore, boils down to the question that oncologists have been struggling with: how high of a VTE risk is worth prophylaxis? A full discussion of this is the subject of my article4 and beyond the scope of this response. I would like, however, to illustrate this struggle by pointing out that in a randomized clinical trial of prophylaxis in patients with pancreas cancer, VTE during treatment declined from 23.0% to 3.4% with prophylaxis (P=.002; NNT, 6).5 These are rates and benefits comparable to myeloma patients. Why, then, do we make one clinical decision in patients with myeloma and another in pancreas cancer?

References:

  • 1.

    Lyman GH, Khorana AA, Kuderer N et al.. Reply to T.H. Oo. J Clin Oncol 2013;31:43814382.

  • 2.

    Khorana AA, Dalal MR, Lin J, Connolly GC. Health care costs associated with venous thromboembolism in selected high-risk ambulatory patients with solid tumors undergoing chemotherapy in the United States. Clinicoecon Outcomes Res 2013;5:101108.

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  • 3.

    Di Nisio M, Porreca E, Ferrante N et al.. Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy. Cochrane Database Syst Rev 2012:CD008500.

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    • Export Citation
  • 4.

    Khorana AA. Venous thromboembolism prevention in cancer outpatients. J Natl Compr Canc Netw 2013;11:14311438.

  • 5.

    Maraveyas A, Waters J, Roy R et al.. Gemcitabine versus gemcitabine plus dalteparin thromboprophylaxis in pancreatic cancer. Eur J Cancer 2012;48:12831292.

    • Search Google Scholar
    • Export Citation
  • 1.

    Lyman GH, Khorana AA, Kuderer N et al.. Reply to T.H. Oo. J Clin Oncol 2013;31:43814382.

  • 2.

    Khorana AA, Dalal MR, Lin J, Connolly GC. Health care costs associated with venous thromboembolism in selected high-risk ambulatory patients with solid tumors undergoing chemotherapy in the United States. Clinicoecon Outcomes Res 2013;5:101108.

    • Search Google Scholar
    • Export Citation
  • 3.

    Di Nisio M, Porreca E, Ferrante N et al.. Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy. Cochrane Database Syst Rev 2012:CD008500.

    • Search Google Scholar
    • Export Citation
  • 4.

    Khorana AA. Venous thromboembolism prevention in cancer outpatients. J Natl Compr Canc Netw 2013;11:14311438.

  • 5.

    Maraveyas A, Waters J, Roy R et al.. Gemcitabine versus gemcitabine plus dalteparin thromboprophylaxis in pancreatic cancer. Eur J Cancer 2012;48:12831292.

    • Search Google Scholar
    • Export Citation
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