Fixed dosing: A solution or a new problem?
Efforts to reduce the financial impact of discarded cancer drugs can blow back on physicians, patients, and payers in other unanticipated ways. Take fixed dosing. Although chemotherapy dosing remains weight-based, many targeted therapies — such as nivolumab and pembrolizumab — recently transitioned to a fixed dosing regimen.
Administering a fixed, instead of weight-based, dose eliminates waste but can create new problems.
“Patients with cancer not only tend to get too high a dose of the drug, but costs go up significantly,” said Dr. Goldstein. In a 2017 analysis, Dr. Goldstein and colleagues compared dosing strategies in patients with metastatic non–small cell lung cancer who received pembrolizumab. The team found that the total annual cost of weight-based dosing was $2.6 billion, whereas the cost of the fixed dosing strategy was $3.44 billion — 24% more. In other words, personalized weight-based dosing would save more than $825 million dollars in the United States each year.
A 2020 analysis based in France found a similar cost increase of 26% for fixed dosing of pembrolizumab as well as nivolumab.
“I’ve argued we should go back to weight-based dosing,” Dr. Goldstein said. “Why should we give a higher dose with the same efficacy when that dose will cost significantly more and has the potential to increase adverse events?”
Does dose rounding work?
Rose DiMarco, PharmD, BCPS, BCOP, keeps a tight watch on patients being treated at the Sidney Kimmel Cancer Center at Jefferson Health in Philadelphia.
Dr. DiMarco educates patients about their treatment plan, reviews their lab results, and monitors them for side effects and drug interactions.
She also thinks a lot about costs.
“We spend about $100,000 a day on oncology drugs, and we want to make sure we’re not being wasteful,” Dr. DiMarco said in an interview.
One major initiative to curb waste and reduce costs at Jefferson has centered on dose rounding, which calculates whether a specific dose can be altered slightly to conserve vials and prevent waste. According to the Hematology/Oncology Pharmacy Association, a patient can receive up to 10% more or less of a weight-based dose without impacting treatment efficacy.
If, for instance, a patient requires 380 mg, but two vials come to 400 mg, rounding up that dose by approximately 5% means eliminating 20 mg that would go unused. But if that patient requires 420 mg, rounding down about 5% means substantial savings from not opening a new vial.
At Jefferson, Dr. DiMarco and her pharmacy colleagues map out dose ranges for all patients. Anyone who falls inside the 10% may be eligible for dose rounding. Anyone who doesn’t will receive the usual dose.
Although it is a challenge to implement, dose rounding has become standard of care at many cancer centers across the United States and is linked to substantial savings.
A 2018 analysis projected annual savings of $865,000 associated with rounding down eight monoclonal antibodies for patients with metastatic disease at a community cancer center. A more recent analysis from the Mayo Clinic found that dose rounding saved a total of 9,814 drug vials — 4485 of which were cancer drugs and 5329 of which were biologics — and resulted in $7.3 million in savings over 6 months in 2019 — $1.56 million from oncology agents and $5.7 from biologics.
And in a small 2019 analysis, researchers at Jefferson showed dose rounding of one monoclonal antibody saved approximately $30,000 in just 3 months, Dr. DiMarco noted.
“Not only does this process reduce costs and waste, but it also standardizes the preparation of hazardous medications, which can help prevent medication errors,” Dr. DiMarco said.
Nibbling around the edges
Despite estimates that scale into the billions of dollars, “drug wastage is just a small part of overall cancer costs,” Dr. Sarfaty said.
Fumiko Chino, MD, a radiation oncologist at MSK, agrees. “When we talk about affordability and cost, we can nibble around the edges of what’s really important,” Dr. Chino said. “Discarded drugs may cost a lot when you consider them in aggregate, but they are not as important as negotiated drug prices, which could substantially reduce overall costs.”
And until drug prices are addressed on a broader policy level, the cost of cancer care likely won’t improve in a meaningful way.
“But for the patient sitting in front of me, my focus will always be to provide the best care possible,” Dr. Binder said.
A version of this article first appeared on Medscape.com.