Substantial Spending on Cancer Drugs Without Survival Benefit

Roxanne Nelson, RN, BSN

October 22, 2021

The cost of cancer drugs without documented survival benefit is being highlighted again. In this latest study, the focus is on oral targeted drugs for cancer and their use in the 'real world.' 

The team calculated use and spending on these drugs by US residents with employer-sponsored insurance between 2011 and 2018.

They also divided the 44 oral targeted drugs and cancer indications into two groups: those with proven survival benefit and those without. The cumulative spending was slightly greater for drugs without proven survival benefit ($1.8 billion vs $1.7 million for drugs with a documented overall survival benefit).

"Our findings suggest that cancer drugs with major shortcomings in their evidence base are adopted in the health system and account for substantial spending," they conclude.

The study was published in the October 18 issue of JAMA Internal Medicine.

Another study published alongside looked at Medicare spending on cancer drugs without survival benefit, as reported earlier this week by Medscape Medical News.  

"Increasing use of, and spending on, cancer drugs without documented overall survival benefit reflects characteristics of the US cancer drug ecosystem, which includes drug development, regulation, pricing, advertising, and reimbursement," commented senior author of both studies, Anita Wagner, PharmD, MPH, DrPH, associate professor of population medicine at the Harvard Pilgrim Health Care Institute and Harvard Medical School, Boston, Massachusetts.

"Policy changes in this complex ecosystem likely need to be multipronged and are likely challenging and controversial as most require cooperation of stakeholders with different priorities," she said.

However, some changes to this system may be more readily feasible than others, she pointed out.  

"Among those may be FDA efforts to make explicit and easily accessible for patients, their clinicians, and others what is known and what is not known about the clinical benefits of newly approved, highly priced cancer drugs," Wagner told Medscape Medical News. "Such efforts could start with consistent documentation of overall survival information in FDA-approved labeling as we have suggested, and clear visual alerts in labels of limited evidence underlying accelerated approvals akin to black box warnings."

Documented Survival Benefit Lacking

In this study, Wagner and colleagues focused on 44 oral targeted cancer drugs.

More than three quarters of the drugs (n = 34, 77.3%) were approved with the support of at least one randomized controlled trial for at least one indication. The other 10 drugs (22.7%) were approved on the basis of single-arm studies or noncomparative trials alone.

However, only 11 drugs (25%) had documented, statistically significant overall survival benefit for at least one indication, and only 4 drugs (9%) had overall survival as the primary endpoint in a pivotal randomized controlled trial.

Among the top 20 dugs (by spending), only one was not backed by a pivotal randomized controlled trial but 13 lacked survival data. Within this group, 15 drugs had orphan drug designations, and 6 were granted breakthrough therapy designation, 10 had been approved under fast track, 15 drugs under priority review, and 8 drugs under accelerated approval pathways.

"Patients may not be aware of what is known and what is not known about a new cancer medicine, both in terms of benefits and risks," cautioned Wagner.  "More research is needed on the extent to which patients, clinicians, and the public understand what is known and what is not known about the clinical benefits of newly approved cancer drugs and the tradeoffs of individual and societal spending on drugs without documented overall survival benefit."

Strategies Available to Slow the Trend

Approached for comment on the new studies, Aaron Mitchell, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City, outlined the issues.  

"There are two sides of the coin — the high prices and the generally unimpressive effectiveness," he said. "There are approaches that would deal with one or the other of these, or both together."

Strategies that would at least stem the tide of rising prices have already been discussed. "One of them would be to allow Medicare to negotiate drug prices," he told Medscape Medical News. "Unfortunately this is politically difficult because of the power of the pharmaceutical industry lobby."

Another approach would be to decouple FDA approval and Medicare coverage. "Right now, every cancer drug that the FDA approves, Medicare is required to pay for at whatever price pharma decides to set," Mitchell noted. "If Medicare were allowed to say 'thanks but no thanks' to excessively expensive drugs — even FDA-approved ones — then the drug industry would have to lower their prices in response."

As far as the issue of drug effectiveness, the easy solution here is just to raise the standards for FDA approval, he pointed out. At present, accelerated approvals are granted on surrogate endpoints such as response rates, without the drug having documented clinical benefit such as improved progression-free or overall survival.

"Critics of this approach fear that raising the bar for approval would cause us to 'miss' game-changer drugs, but this is backwards thinking," Mitchell said. "Truly game-changing drugs will meet any bar, including improving overall survival. But by lowering the bar, we do not get more game-changers, we just get more of the marginal drugs that can only meet that lower bar."

No outside funding was reported for the study. Wagner disclosed that her work is partly funded by the American Cancer Society, and she reported receiving grants from the American Cancer Society outside the submitted work. Several co-authors report relationships with industry as noted in the paper. Mitchell has disclosed no relevant financial relationships.

JAMA Intern Med. Published online October 18, 2021. Abstract

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