Study challenges high cancer drug doses; lower amounts may be just as effective

• Patients are being overtreated with cancer drugs, as evidence suggests lower doses are often just as effective with fewer side effects.
• A study estimated $31 billion could have been saved in 2024 alone through dose optimization, but financial incentives for drugmakers and hospitals block this research.
• The FDA’s “Project Optimus” promotes lower-dose studies, but the agency lacks legal power to force drugmakers to test reduced dosages post-approval.
• Fewer than half of cancer drugs approved since 2000 have proven to extend survival, while the median price has quadrupled to $25,000 per month.
• Patient advocates demand informed consent, arguing people deserve plain facts about a drug’s true benefits and costs before risking their savings and health.

Why are cancer patients being prescribed FDA-approved doses that may be far higher than necessary? A recent investigation by KFF Health News highlights a growing movement of researchers and doctors challenging standard dosing protocols for expensive immunotherapies and other cancer drugs. Their work suggests many patients could receive lower or less frequent doses, reducing side effects and saving billions in healthcare costs without compromising outcomes. Oncologists worldwide are finding that less can be more, raising questions about the financial incentives baked into current prescribing practices.

A patient’s gamble prompts a wider look at dosing

Economist Chuck Manski’s decision to stop his immunotherapy treatment early, due to severe side effects, is a case in point. After six months of nivolumab (Opdivo) for advanced melanoma in 2022, Manski faced a year-long FDA-recommended protocol. His oncologist could not explain why a full year was optimal, leading Manski to research the issue himself and ultimately stop treatment. He showed no signs of cancer at the time.

Manski’s experience is echoed by doctors elsewhere. In India, oncologists report using as little as one-twelfth of the labeled nivolumab dose with powerful results against several cancers. Clinical trials in Europe are also testing whether a 50% reduction in standard nivolumab doses can be just as effective for lung cancer patients.

Profit motive cited as a barrier to lower-dose research

Critics argue the primary obstacle to dose-optimization studies is financial. Drug companies earn more revenue from higher doses, and providers benefit too. A federal program lets hospitals buy drugs at a discount while charging insurers more, and doctors receive a percentage of the drug’s price for each infusion.

One study estimated that using minimum necessary dosages for 29 expensive cancer drugs could have saved the U.S. healthcare system roughly $31 billion in 2024 alone. That financial reality discourages research into lower doses once a drug reaches the market. One breast cancer researcher says she often starts patients on lower doses of Kisqali to avoid severe side effects — but insurers routinely challenge those prescriptions, likely because rebates are tied to the standard dosage.

Merck defends its dosing for pembrolizumab (Keytruda), saying it’s based on extensive testing and that unstudied changes could compromise effectiveness. A University of Chicago oncologist counters that the profitability of such drugs for hospitals is precisely why no one is rushing to test lower amounts.

FDA’s push for better dosing faces limits

The FDA has acknowledged the issue, launching “Project Optimus” in 2021 to encourage more precise dosing studies before approval. Health and Human Services says the agency has since approved lower, less toxic doses for four lung cancer drugs. But by law, the agency generally has no power to force drugmakers to study lower dosages once a drug is already approved and on the market.

Trials are now underway comparing standard nivolumab against lower doses, and testing whether breast cancer patients can start on reduced doses of Kisqali and Ibrance. For patients like Allegra Warfield, who suffered severe side effects and faced prohibitive costs, the lack of clear guidance has been a serious problem; she was left researching her own treatment online.

Patients say they deserve the full picture

A Bloomberg analysis found that fewer than half of cancer drugs approved since 2000 have been shown to extend survival, while the median price of new cancer drugs has quadrupled to roughly $25,000 a month — partly because the FDA allows approval based on preliminary tumor-shrinkage data rather than proof that patients live longer. Ibrance, approved in 2015, has generated over $40 billion in sales despite a 2022 study finding no statistically meaningful survival benefit for its main use — a detail buried deep in the drug’s label.

Patient advocates argue this is ultimately a question of informed consent: people facing cancer deserve to know, in plain terms, what a drug will and won’t do for them before they commit to a regimen that could cost them their savings and their health — regardless of whether that information helps the bottom line.

Sources for this article include:

ChildrensHealthDefense.org

PharmaReformAlliance.com

Bloomberg.com