番茄社区

More people than ever were on new cancer drugs backed by relatively weak evidence, and the money spent on these pricey drugs exceeded that of dollars spent on those with a known overall survival (OS) benefit, according to commercial claims data as of this year.

Of 37,348 U.S. patients receiving one of 44 new oral targeted cancer drugs, the proportion receiving drugs without documented OS benefit rose from 12.7% in 2011 to 58.8% in 2018.

By the end of 2018, the $1.8 billion spent on oral cancer drugs without an OS benefit eclipsed the $1.7 billion on better-proven therapies, the study group led by Anita Wagner, PharmD, MPH, DrPH, of Harvard Medical School in Boston, reported.

Only 11 of the 44 drugs had a documented statistically significant OS benefit in their FDA-approved labels by the end of 2018. For these 11 oral cancer drugs, the OS benefit ranged from 4.6 to 6.6 months. None of the drugs had documented quality-of-life benefits. (Since that time, some of the other 33 drugs on the list have established an OS benefit, however.)

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

Although it would be hard to overhaul this complex system, some changes are feasible, Wagner wrote in an email to 番茄社区.

"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," she said, suggesting that the FDA label cancer drugs more clearly with OS information and add visual alerts to denote accelerated approvals.

In the thought to be "reasonably likely" to predict clinical benefit, more and more cancer drugs are being approved based on surrogate endpoints, such as progression-free survival or response rate, as permitted by the FDA's .

Wagner's team reported that 40 of the 44 oral cancer drugs analyzed in the study had been approved by one such expedited pathway:

• 32 drugs had an orphan drug designation
• 21 had first indications approved under the fast track pathway
• 34 were approved under the priority review pathway
• 16 were approved under the accelerated approval pathway
• 15 had breakthrough therapy designation

The approval of 34 of 44 drugs was supported by at least one randomized controlled trial. Ten drugs were approved based on trials without a control group.

Past studies have illustrated how the U.S. is particularly lenient when it comes to approving cancer drugs -- a phenomenon derided as "onco-exceptionalism" by critics.

"'Onco-exceptionalism' in drug development, approval, pricing, and coverage raises questions at the individual patient level of care quality and at the societal level of allocation of resources," Wagner and colleagues wrote. "In addition, because it incentivizes development of new drugs similarly lacking evidence of benefit in the largest pharmaceutical market, onco-exceptionalism may negatively affect cancer patients worldwide."

Study authors had examined dispensing claims from the from 2011 to 2018. The study included 37,348 de-identified patients with employer-sponsored health insurance who received at least one of 44 new oral targeted cancer drugs (three cancer drugs approved in late 2018 were omitted from the study due to a lack of any dispensing claims).

Of the study population, 57.1% were men, and the mean age was 64.1 years.

The authors cautioned that as this study only included privately insured patients, it failed to account for oral cancer drug use by publicly insured and uninsured patients.

Nevertheless, Medicare alone had spent an estimated $569 million from 2017 to 2019 on four intravenous cancer drugs -- atezolizumab (Tecentriq), durvalumab (Imfinzi), nivolumab (Opdivo), and pembrolizumab (Keytruda) -- that had accelerated approval indications ultimately reevaluated by the FDA starting in December 2020, according to a by Wagner's group in the same issue of JAMA Internal Medicine.

"This reevaluation resulted in voluntary manufacturer withdrawals of atezolizumab for urothelial cancer, durvalumab for urothelial cancer, and nivolumab and pembrolizumab for [small cell] lung cancer," Wagner and colleagues noted.

"The magnitude of spending estimated in our study highlights the need for the FDA to withdraw approvals for drug indications with a confirmed lack of clinical benefit in a timely manner," they concluded.

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