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STAT – The latest look at FDA’s breakthrough designation finds no benefits from cancer meds

STAT – The latest look at FDA’s breakthrough designation finds no benefits from cancer meds

The idea of a breakthrough therapy was promoted to speed approvals of medicines that held promise for treating a life-threatening disease and demonstrated substantial improvement over existing drugs. However, a new study finds that while cancer drugs considered to be breakthroughs were approved more quickly, they were not safer, more novel, or more effective than drugs not given this designation.


The study examined 58 new cancer medicines that were approved by the Food and Drug Administration between 2012 and 2017. Of these, 25 — or 43 percent — received breakthrough therapy designation. The median time to a first FDA approval was 5.2 years for drugs that given a breakthrough designation versus 7.1 years for cancer medicines that were not considered to be breakthroughs.


Meanwhile, breakthrough designations did not yield statistically significant differences in median gains in progress-free survival, the response rate of solid tumors to treatment, relying on a novel mechanism of action, or the subsequent rates of death or side effects, according to the study, which was published in the Journal of Clinical Oncology.


“Our study shows that among cancer drugs, the breakthrough label does not necessarily translate to better patient outcomes,” Dr. Aaron Kesselheim, a co-author and Harvard Medical School professor, writes us. “There needs to be enhanced post-approval monitoring of so-called breakthrough therapy drugs to assess whether they ever live up to their original hype, but that’s not part of the pathway.”


The study noted that cancer treatments represented 54 percent of the new drugs with a breakthrough designation and approved by the FDA from the program’s inception in 2012 through December 2017 — or 25 of 46 drugs. By comparison, cancer medications represented 26 percent of all new drugs were approved during that period, or 58 of 221 treatments.


The authors further contended breakthrough designations can create false expectations among doctors and patients, since rigorous evidence may not become available for several years, if at all. As an example, the study cited a 2015 survey in which 86 percent of nearly 600 American adults believed that a hypothetical lung cancer drug described as a breakthrough was more effective than other drugs.


Consequently, the authors argued that such interpretations may further fuel health care costs. As new cancer medications are slapped with ever-rising price tags, they maintain that access to “high quality information” about risks and benefits of treatments should be a priority so patients and physicians can make appropriate decisions about care.


“By labeling new cancer drugs as breakthroughs, when actual benefit is neither large nor supported by robust data, the pathway is creating expectations among seriously ill patients that are unlikely to be fulfilled,” Dr. Jonathan Darrow, a co-author and Harvard Medical School professor, writes us. “The term breakthrough may also be used to justify exceptionally high prices that are out of proportion to actual therapeutic value.”


The conclusions come amid on-again, off-again debate over the validity of breakthrough designations, which was renewed last month, in fact, courtesy of a different paper by Kesselheim and Darrow, among others. In that analysis, they reviewed 31 drugs designated as breakthroughs between 2014 and 2016, but found some medicines may significantly help patients while the benefits of others were unclear.


Both analyses were met with derision by Jeff Allen, who heads Friends of Cancer Research, an advocacy group. In a recent essay, he labeled the previous analysis, which appeared in The New England Journal of Medicine, as “tone deaf.” And he defended breakthrough designations for providing patients with “tremendous benefit” since it was passed into law in 2012.


In response to the latest paper, Allen wrote us that, “if the authors are suggesting that any of the breakthroughs should have been slowed in their development — and patients afflicted by those diseases would have been better off from that two year delay — they are simply misguided.


“It is unclear what the concern is from their paper,” he continued. “These products meet the same standards of safety and efficacy — they just do it faster — and that’s a good thing for people fighting cancer who don’t have other options.”


So what do the authors of the latest study suggest? They conclude by saying that “continued follow-up, rigorous confirmatory studies, and more robust and transparent criteria for breakthrough designation are needed” in order to “distinguish true breakthroughs from those that are breakthroughs in name only.”


We should note that financing for the study was provided by the John and Laura Arnold Foundation, which underwrites an increasing amount of research into prescription drug pricing, pharmaceutical industry behaviors, and regulatory dictums. The foundation also underwrote the recent piece that appeared in the New England Journal of Medicine.…