Oncology drugs that were recommended on an off-label basis by the National Comprehensive Cancer Network® Clinical Practice Guidelines in Oncology (NCCN Guidelines®) were in fact supported by actual data, reported a study recently published online in the Annals of Oncology.1

The paper comes after a 2018 retrospective study by senior author Vinay Prasad, MD, PhD, Oregon Health and Science University, Portland, and colleagues, which evaluated the level of evidence for off-label drug recommendations in oncology that are listed in the NCCN Guidelines.2 That study concluded that the NCCN guidelines “frequently” recommend “beyond” the US Food and Drug Administration (FDA)-approved indications and described the strength of evidence supporting the existing off-label recommendations as “weak.”2

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The current study investigated the 44 off-label recommendations listed in the NCCN Guidelines that were identified in the aforementioned 2018 study. The analysis revealed that 14 of the 44 indications that were considered off label were eventually approved by the FDA and/or were backed by evidence from randomized controlled trials (RCTs), and 8 indications were “minor extrapolations” from the drug label. Also, 5 of the 44 recommendations were, in fact, on-label recommendations.

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The remaining 17 off-label extrapolations were based on “lower-level” data, according to the authors. Of these 17 recommendations, 8 indications were for mechanism-based drugs used for patients with rare cancers or who had limited treatment options; 7 extrapolations were based on non-RCTs that showed “significant efficacy,” that is, a more than 50% response rate for an agent; and 2 extrapolations were eventually removed from the NCCN Guidelines because newer treatments emerged that were more effective and/or had a better safety profile.

The authors of the prior 2018 study “claimed that 36% of these recommendations were made with no evidence given.” But, the authors of the 2019 study wrote that their analysis “found that 100% of the off-label recommendations were supported by data.”


  1. Kurzrock R, Gurski LA, Carlson RW, et al. Level of evidence used in recommendations by the National Comprehensive Cancer Network (NCCN) guidelines beyond Food and Drug Administration approvals. Ann Oncol. doi: 10.1093/annonc/mdz232
  2. Wagner J, Marquart J, Ruby J, et al. Frequency and level of evidence used in recommendations by the National Comprehensive Cancer Network guidelines beyond approvals of the US Food and Drug Administration: retrospective observational study. BMJ. 2018;360:k668