US Cancer Drug Approvals Ensure Access but Not Value

Cancer drugs that have been approved in the United States are often not immediately approved in the United Kingdom and Canada, owing to uncertainty over benefits and harms as well as extremely high prices, two new studies in JAMA Internal Medicine indicate.

The oncology drug approval process of the US Food and Drug Administration (FDA) is “broken,” concludes an accompanying editorial.

“Many cancer drugs come to market in the United States and, eventually, globally at unaffordable prices with massive uncertainty about their benefits and harms,” say the editorialists, Vinay Prasad, MD, MPH, University of California, San Francisco, and Myung Kim, MD, Oregon Health and Science University, Portland, Oregon.

“The US system of approval of drugs with uncertain clinical benefit followed by mandated coverage by Medicare without any ability to negotiate on prices ensures access,” they observe.

“It is less clear that the US system benefits patients with cancer,” they conclude.

In addition, the uptake of these cancer drugs “is often delayed in high-income Western nations because of justified and persistent doubts about value,” they continue.

“We should consider the possibility that our drug policy has negative repercussions for patients with cancer worldwide,” they write.

Negative Repercussions

The negative repercussions of the FDA drug approval process were most evident in the study from Canada. As analyzed by Daniel Meyers, MD, University of Calgary, Alberta, Canada, and colleagues, between 2011 and 2020, the pan-Canadian Oncology Drug Review (pCODR) issued 104 reimbursement recommendations for cancer drugs that were indicated for solid tumors.

“Three-quarters of all submissions received a positive recommendation,” the investigators report. However, more than 92% of those approvals were conditional, most commonly because of serious reservations about the cost-effectiveness of the drug, they note.

Moreover, only half of cancer drugs recommended by pCODR improved overall survival (OS), and survival gains were usually modest. The median OS was only 3.7 months, and the median progression-free survival (PFS) was only 4.7 months; these rates are not substantially different from those of drugs that received a negative recommendation, Meyers and colleagues point out.

Importantly, almost 40% of cancer drugs that received a positive recommendation from pCODR did not achieve the threshold for substantial clinical benefit, as assessed by the European Society for Medical Oncology–Magnitude of Clinical Benefit Scale.

These results suggest that despite the pCODR framework, which provides reimbursement recommendations based on clinical benefit, cost-effectiveness, and patient-based values, “cancer drugs without meaningful patient benefit continue to be reimbursed in the Canadian market,” the authors conclude.

In the UK study, Avi Cherla, MSc, London School of Economics and Political Science, London, the United Kingdom, and colleagues compare cancer drug indications that received FDA accelerated approval from December 1992 to May 2017 with the same indications in England through August 2019.

Of 93 cancer drug indications that received FDA accelerated approval over the past 25 years, they found that 30 drug indications were not reviewed for coverage by the UK’s National Health Service (NHS). In addition, 12 drug indications were denied authorization or coverage by either European regulators or the National Institute for Health and Care Excellence (NICE) because of insufficient safety, clinical efficacy, or cost-effectiveness data.

Furthermore, NHS coverage of cancer drugs that did receive FDA accelerated approval frequently required additional price concessions, restriction of drug indications to specific patient subgroups, and the collection of additional data. As has been reported, most drug approvals by the FDA are based on surrogate markers, such as tumor shrinkage or delayed tumor growth (PFS), a point that editorialists Prasad and Kim emphasize.

“Surrogate end points result in substantial uncertainty regarding the magnitude of clinical benefit (if any exists), which is a key input to a cost-effectiveness calculation,” they point out.

Perhaps most importantly, “the cancer drugs available in England, Canada, and the US are not as good as physicians would hope for patients,” the editorialists write. For example, only 34 of 52 cancer drugs evaluated by NICE showed any survival benefit, and that benefit was at best very modest.

JAMA Intern Med. Published online February 22, 2021. Canadian study, Abstract; UK study, Full text; Editorial

The study authors have disclosed no relevant financial relationships. Prasad has received grants from Arnold Ventures Research and personal fees from Johns Hopkins Press, Medscape, UnitedHealthcare, New Century Health, and Evicore. He has also received honoraria from medical centers, nonprofit organizations, and professional societies and hosts a podcast called Plenary Session that has Patreon backers.

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