Prescribing of Off-Label Chemotherapy Is Common, and Most Off-Label Drug Use Meets NCCN Compendium Criteria  

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Off-label prescribing of drugs remains common in oncology, but about two-thirds of off-label prescribing is consistent with the National Comprehensive Care Network (NCCN) compendium, according to a study1 reviewed at the Best of ASCO® ’13 meeting in Chicago by Monika K. Krzyzanowska, MD, MPH, Princess Margaret Cancer Centre University of Toronto. “The investigators were interested in characterizing appropriate drug use and, specifically, addressing whether oncologists were choosing wisely when it came to drug therapy,” Dr. Krzyzanowska explained.

Study Details

The investigators used the SEER (Surveillance, Epidemiology and End Results)-Medicare database to analyze use of intravenous chemotherapy drugs among 42,634 Medicare beneficiaries diagnosed with metastatic cancer between 1998 and 2008. Each drug was classified according to whether it had an indication approved by the Food and Drug Administration (FDA), based on NCCN compendia guidelines, or neither of these. “The NCCN compendium is recognized as an authoritative reference for insurance coverage for drug indications without FDA approval,” the investigators stated.

Overall results “show about 45% of patients received at least one unapproved drug,” Dr. Krzyzanowska said. “There was certainly variation between the different sites. For example in colon cancer, the prevalence of off-label use was very low, vs in a disease such as myeloma, the prevalence of off-label use was much higher.” The percentage of patients who received any unproved drug was about 10% for colon cancer and 80% for myeloma.

As background, Dr. Krzyzanowska cited a survey of American oncologists from about 5 years ago, which suggested that the majority of American oncologists have discussed and offered off-label therapy to their patients, although a smaller proportion did so on a routine basis. She also referred to a more recent study published in the Journal of Clinical Oncology,2 which found that off-label use of 10 commonly prescribed intravenous chemotherapies amounted to 30%.

Strengths and Limitations

As strengths of the study, Dr. Krzyzanowska listed the large sample size and insight into temporal trends. The investigators looked at 10 years of data “and interestingly enough, the proportion of off-label use was similar year to year,” she said.

“In terms of limitations, because this was a SEER-Medicare sample, the focus was predominantly on older patients and only on intravenous medications, so I would argue that it does underestimate off-label use, as I suspect that younger patients may be more likely to receive off-label therapy in the metastatic setting,” Dr. Krzyzanowska said. “There was also a lack of information on the motivation for off-label prescribing or the impact in terms of both efficacy and toxicity.”

Sit Back and Scrutinize

The current study adds to the growing literature providing evidence that off-label prescribing in common in cancer patients, but Dr. Krzyzanowska believes that more research needs to be done in this area. “I would really like to see some studies that could show us the benefit side and the toxicity side of off-label prescribing—so really the clinical outcome,” she said.

For now, however, “there is some time to sit back and scrutinize off-label use in practice,” she continued. “I think there are some areas where off-label use has less reason to be done.” As examples, she cited off-label prescribing that is not consistent with the NCCN compendium, as well as off-label prescribing of expensive drugs or “situations where the benefit is likely to be small and risk of toxicity substantial.”

Moving forward, Dr. Krzyzanowska suggested increased physician education about appropriate vs inappropriate off-label uses and decision support for physicians. Heightened patient engagement and public awareness are also very important, she said. Tracking off-label use of drugs and indications would be useful for obtaining more information about particular risk-benefit ratios for specific indications. ■

Disclosure: Dr. Krzyzanowska has an uncompensated consultant or advisory role with Bayer/Onyx, has received honoraria from AstraZeneca, Novartis, and Sanofi, and has received research funding from AstraZeneca and Exelixis.


1. Hershman DL, Neugut AI, Buono D, et al: Off-label and compendia use of chemotherapy in patients with metastatic cancer. 2013 ASCO Annual Meeting. Abstract 6509. Presented August 9, 2013.

2. Conti, RM, Bernstein AC, Villiflor VM, et al: Prevalence of off-label use and spending in 2010 among patent-protected chemotherapies in a population-based cohort of medical oncologists. J Clin Oncol 31:1134-1139, 2013.

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