Postmarketing Label Modifications for Cancer Drugs Approved Without Supporting Randomized Controlled Trials


Key Points

  • Indications without supporting randomized controlled trials were more likely to have postapproval label changes regarding common adverse events and warnings/precautions.
  • No difference in modifications regarding boxed warnings was found. 

In a study reported in the Journal of Clinical Oncology, Shepshelovich et al found that cancer drugs approved by the U.S. Food and Drug Administration (FDA) for treatment of solid tumors without supporting randomized controlled trials were more likely to have postapproval safety-associated label modifications.

Study Details

The study involved a search of the Drugs@FDA website for new drug indications in solid tumors approved between January 2006 and December 2016, with follow-up for label modifications through October 2017.

Indications Without Randomized Controlled Trial Support

A total of 59 individual drugs for 109 solid tumor indications were identified, with 17 indications (15.6%) not supported by a randomized controlled trial. There was no change over the study period in the proportion of indications without randomized controlled trial support. Indications not supported by randomized controlled trials were more likely to require companion diagnostic tests (odds ratio [OR] = 3.90, P = .02), include surrogate endpoints as primary outcomes (OR = 7.88, P < .001), receive Breakthrough Therapy designation (OR = 7.62, P = .006), and receive accelerated approval (OR = 17.67, P < .001).

For indications without vs with randomized controlled trial support, postapproval modifications in common adverse events were significantly more likely (71% vs 29%, OR = 5.78, P = .002), with a borderline significant increase in postapproval major modifications in warnings and precautions (88% vs 62%, OR = 4.61, P = .051) also being observed. No difference was observed for indications with vs without randomized controlled trial support for postapproval major modifications in indication and usage, dosing and administration, boxed warnings, or contraindications.

The investigators concluded, “Cancer drug indications not supported initially by [randomized controlled trials] are associated with more postmarketing safety-related label modifications. Health-care professionals should be vigilant for unrecognized adverse effects when prescribing drugs approved without a supporting [randomized controlled trial].”

Eitan Amir, MD, PhD, of the Division of Medical Oncology, Princess Margaret Cancer Centre, is the corresponding author for the Journal of Clinical Oncology article. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.