Characteristics of FDA-Designated Breakthrough and Nonbreakthrough Cancer Drugs


Key Points

  • No significant difference in progression-free survival gains or severe adverse events was observed for breakthrough-designated vs non–breakthrough-designated drugs.
  • Breakthrough-designated drugs were not more likely to have a novel mechanism of action. 

In a study reported in the Journal of Clinical Oncology, Hwang et al found little difference in the efficacy and safety of U.S. Food and Drug Administration (FDA)-designated breakthrough vs nonbreakthrough cancer drugs and found that breakthrough drugs were not more likely to represent a novel mechanism of action.

Study Details

In the study, time to FDA approval from investigational new drug application, safety and efficacy from pivotal trials, and mechanism of action were analyzed for all new cancer drugs approved by the FDA between January 2012 and December 2017.

During the study period, the FDA approved 58 new cancer drugs; of these, 25 (43%) received a Breakthrough Therapy designation. The median time to first FDA approval was 5.2 years for breakthrough-designated drugs vs 7.1 years for non–breakthrough-designated drugs (difference = 1.9 years, P = .01).

For breakthrough-designated vs non–breakthrough-designated drugs, median progression-free survival gains were 8.6 vs 4.0 months (P = .11), hazard ratios for progression-free survival were 0.43 vs 0.51 (P = .28), and response rates for solid tumors were 37% vs 39% (P = .74). Breakthrough-designated and non–breakthrough-designated drugs had a similar likelihood of having a novel mechanism of action (36% vs 39%, P = 1.00). Rates of death (6% vs 4%, P = .99) and rates of serious adverse events (38% vs 36%, P = 0.93) were similar in pivotal trials of breakthrough-designated and non–breakthrough-designated drugs.

The investigators concluded, “Breakthrough-designated cancer drugs were associated with faster times to approval, but there was no evidence that these drugs provide improvements in safety or novelty; nor was there a statistically significant efficacy advantage when compared with non–breakthrough-designated drugs.”

The study was supported by the Laura and John Arnold Foundation, Harvard Program in Therapeutic Science, and Engelberg Foundation.

Aaron S. Kesselheim, MD, JD, MPH, of the Program on Regulation, Therapeutics, and Law, Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital and Harvard Medical School, 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®.