Cancer Drug Doses Face Growing Questions
Northwestern University economist Chuck Manski has spent much of his career examining how people make decisions when outcomes are uncertain. That experience became particularly useful when he had to make an important choice about his own cancer treatment.
In 2022, Manski underwent six months of monthly infusions of nivolumab, an immunotherapy used to treat advanced melanoma. The treatment severely affected his health. According to Manski, it damaged his thyroid, leaving him dependent on medication for life, while also causing intense dryness in his eyes, lips and mouth.
The treatment plan approved by the US Food and Drug Administration called for patients to receive the drug for a full year. However, Manski said his oncologist was unable to explain why twelve months was considered the appropriate duration. Her explanation was simply that the treatment was FDA approved and therefore was the standard approach.
After six months, Manski had no apparent signs or symptoms of cancer. He also spent considerable time reviewing medical research. Based on what he found, he believed that the serious side effects indicated that the treatment had likely already achieved most of its potential benefit.
Manski ultimately decided to stop treatment on his own. He said nobody was able to tell him that continuing for a full year represented the ideal treatment duration.
Different Countries Use Different Doses
Manski’s decision reflected treatment practices already being explored in countries including Canada, Israel and Sweden. Doctors in those countries have used lower doses of nivolumab, which is marketed as Opdivo, as well as another immunotherapy drug called pembrolizumab, sold as Keytruda.
In some cases, doctors have also shortened treatment periods or increased the time between doses compared with recommendations in the United States.
Research from India has raised even more questions about dosing. Oncologists there found that doses of nivolumab as low as one twelfth of the labeled amount could have a strong effect against several types of cancer.
Manski argues that there remains significant uncertainty over how much of these medicines patients actually need.
His own experience led him to become involved with a growing group of researchers, doctors and patients who want more research into cancer drug dosing. Their goal is to determine whether some patients could receive smaller doses or shorter courses without reducing the effectiveness of treatment.
Supporters of additional research say such changes could potentially reduce serious side effects while saving billions of dollars in healthcare spending.
Financial Incentives Complicate the Debate
Pembrolizumab is generally given at a standard fixed dose. Nivolumab may also be prescribed at a fixed dose or calculated according to a patient's weight.
Using less medication can mean lower revenue for drug manufacturers. However, financial incentives can also affect hospitals and doctors involved in administering these treatments.
A federal initiative known as the 340B program was introduced in 1992 to help support healthcare for lower income patients. Hospitals that meet certain requirements can purchase medicines at substantial discounts while receiving higher payments from insurers or patients.
Medicare also provides doctors with an additional payment equal to 6 percent of a drug's average price for every infusion.
Research by Aaron Mitchell of Memorial Sloan Kettering Cancer Center found that revenue from cancer drugs received by doctors and hospitals rose dramatically between 2010 and 2024. It increased from approximately $9 billion to almost $36 billion.
Around half of that revenue came from immunotherapy medicines such as pembrolizumab and nivolumab.
Mark Ratain, a professor of medicine and chief hospital pharmacologist at University of Chicago Medicine, said the financial importance of pembrolizumab to American hospitals helps explain why there has been limited enthusiasm for trials examining lower doses.
Drugmakers Defend Existing Recommendations
Merck, which produces pembrolizumab, defended the current dosing recommendations. Company spokesperson Julie Cunningham said the recommended dosage was established through extensive testing.
She argued that determining the appropriate dose for a cancer treatment requires carefully designed clinical trials because cancer is a serious and complex disease.
According to the company, changing the dose or treatment duration without comparable clinical research could potentially reduce the medicine's therapeutic benefit.
The debate therefore continues over whether current cancer drug doses always represent the most effective balance between treatment benefits, side effects and cost, or whether further research could identify safer and more economical approaches for some patients.