Patients and Doctors Push to Test Lower Doses of Costly Cancer Drugs

For six months in 2022, Northwestern University economist Chuck Manski received monthly infusions of nivolumab, sold as Opdivo, for advanced melanoma. The U.S. Food and Drug Administration's (FDA) protocol called for a full year, but Manski stopped once he showed no signs of cancer — the drug had damaged his thyroid, requiring lifelong medication, and left his eyes, lips and mouth severely dry. Neither he nor his oncologist could explain why a year was optimal; she said only that it was FDA-approved, "so that's what we use."

Manski's decision echoed doctors in Canada, Israel and Sweden, who already give lower or shorter doses of nivolumab and the similar drug pembrolizumab (Keytruda) than U.S. labels recommend. In India, oncologists found that as little as one-twelfth of the labeled nivolumab dose had a powerful impact on several cancers. Manski has since joined a growing group of researchers, doctors and patients pushing for dose-optimization studies of costly cancer drugs.

Cost adds pressure: a KFF survey found 43% of U.S. adults skipped medication last year due to cost, and a 2022 Vanderbilt University study found 30% of Medicare cancer drug prescriptions went unfilled. One study of 29 expensive cancer drugs estimated the U.S. could have saved roughly $31 billion in 2024 using minimum necessary dosages. "Decisions aren't always made with the best needs of the patients in mind. The bottom line is another reason," said Dr. Matthew Goetz of the Mayo Clinic Comprehensive Cancer Center.

The drugs are lucrative: Merck sold nearly $32 billion of pembrolizumab last year — FDA-approved for more than 40 cancer conditions and about half of Merck's drug sales — while Bristol Myers Squibb brought in $10 billion from nivolumab. "Pembrolizumab is the lifeblood of American hospitals," said Dr. Mark Ratain of University of Chicago Medicine. Dr. Kathy Miller of Indiana University School of Medicine gives metastatic breast cancer patients 400 milligrams of Kisqali daily, three weeks on, one week off, instead of the labeled 600 milligrams; insurers often challenge her lower-dose prescriptions, she said.

Merck spokesperson Julie Cunningham said dosage recommendations are based on extensive testing, and that changes not similarly studied "may potentially compromise the therapeutic effect."