Level of evidence used in recommendations by the National Comprehensive Cancer Network (NCCN) guidelines beyond Food and Drug Administration approvals

R. Kurzrock, L. A. Gurski, R. W. Carlson, D. S. Ettinger, S. M. Horwitz, S. K. Kumar, L. Million, M. Von Mehren, A. B. Benson

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Background: A previous analysis of 113 National Comprehensive Cancer Network® (NCCN®) recommendations reported that NCCN frequently recommends beyond Food and Drug Administration (FDA)-approved indications (44 off-label recommendations) and claimed that the evidence for these recommendations was weak. Methods: In order to determine the strength of the evidence, we carried out an in-depth re-analysis of the 44 off-label recommendations listed in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Results: Of the 44 off-label recommendations, 14 were later approved by the FDA and/or are supported by randomized controlled trial (RCT) data. In addition, 13 recommendations were either very minor extrapolations from the FDA label (n = 8) or were actually on-label (n = 5). Of the 17 remaining extrapolations, 8 were for mechanism-based agents applied in rare cancers or subsets with few available treatment options (median response rate = 43%), 7 were based on non-RCT data showing significant efficacy (>50% response rates), and 2 were later removed from the NCCN Guidelines because newer therapies with better activity and/or safety became available. Conclusion: Off-label drug use is a frequent component of care for patients with cancer in the United States. Our findings indicate that when the NCCN recommends beyond the FDA-approved indications, the strength of the evidence supporting such recommendations is robust, with a significant subset of these drugs later becoming FDA approved or supported by RCT. Recommendations without RCT data are often for mechanism-based drugs with high response rates in rare cancers or subsets without effective therapies.

Original languageEnglish (US)
Pages (from-to)1647-1652
Number of pages6
JournalAnnals of Oncology
Volume30
Issue number10
DOIs
StatePublished - Oct 1 2019

Keywords

  • guidelines
  • off-label drug use
  • oncology

ASJC Scopus subject areas

  • Hematology
  • Oncology

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    Kurzrock, R., Gurski, L. A., Carlson, R. W., Ettinger, D. S., Horwitz, S. M., Kumar, S. K., Million, L., Von Mehren, M., & Benson, A. B. (2019). Level of evidence used in recommendations by the National Comprehensive Cancer Network (NCCN) guidelines beyond Food and Drug Administration approvals. Annals of Oncology, 30(10), 1647-1652. https://doi.org/10.1093/annonc/mdz232