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Alternative pembrolizumab, nivolumab dosing methods decrease cost
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CHICAGO — An alternative dosing strategy of pembrolizumab and nivolumab may substantially reduce pharmaceutical costs without compromising efficacy in treating various cancers, according to results of a retrospective study presented at ASCO Annual Meeting.
Pembrolizumab (Keytruda, Merck) and nivolumab (Opdivo, Bristol-Myers Squibb) are a major source of cancer drug spending, combined sales for which exceeded $14 billion in 2018. Further, 43.6% of patients with cancer in the U.S. are estimated to be eligible for checkpoint inhibitor therapy.
“I work mainly in our melanoma clinic and that was one of the diseases for which these drugs were first used. For a long time, the dosages of these drugs were weight-based; that was just how we prescribed them,” Evan T. Hall, MD, fellow in the division of oncology at Stanford University School of Medicine, said in an interview with HemOnc Today. “Then, from about 2016 to 2017, new approvals for these drugs began to be for fixed dosing. So now, if you look at the current label for pembrolizumab, it’s fixed dosing at 200 mg for all indications. The original weight-based dose was 2 mg/kg, so the conversion to fixed-dose presumes a body weight of 100 kilograms, which is far more than most of our patients with cancer weigh.”
Fixed dosing of pembrolizumab and nivolumab increases drug spending, Hall said during his presentation. For example, fixed-dose pembrolizumab may increase spending by approximately $825 million per year for lung cancer in the U.S.
Although data suggest weight-based dosing has similar efficacy as fixed dosing, weight-based dosing strategies can result in waste costing more than $1.8 billion from partially used vials.
Thus, Hall and colleagues proposed a “dose-minimization” scheme, where patients would be treated with weight-based dosing but capped at the currently approved fixed dose for each drug.
Researchers retrospectively reviewed data from Stanford to identify all outpatient doses — which included 1,029 doses for 271 patients — of single-agent pembrolizumab or nivolumab administered across cancer types between July 1 and Oct. 31, 2018.
Hall and colleagues modeled the effects of weight-based vs. fixed dosing strategies (for pembrolizumab, 2 mg/kg vs. 200 mg every 3 weeks; for nivolumab, 3 mg/kg vs. 240 mg every 2 weeks or 6 mg/kg vs. 480 every 4 weeks). They also assessed the impact of vial sharing between patients treated at the same location and date, which would reduce drug waste. Cost estimates were established using average sales prices from CMS for Part B drugs.
For most doses in their study period, researchers found that the weight-based dose amount was lower than the fixed dose (77%; n = 789), with a mean patient weight of 76.3 kg. The vast majority of the doses (over 90%) were prescribed as fixed dose.
Dose minimization without vial sharing yielded approximately 9% reduction in usage for nivolumab, equating to a savings of $0.3 million, but only minimal savings for pembrolizumab (–0.7%; –$0.05 million), with the difference largely attributable to limited available vial sizes for pembrolizumab.
Allowing vial sharing led to significant 17.3% reduction in overall spending for pembrolizumab, equating to $1.11 million, while having minimal impact on nivolumab utilization (–9.4%; –$0.31 million).
Under the dose-modification and vial-sharing scenario, savings were estimated at more than $1.4 million (approximately 15%) for the two drugs over the 4-month study period. More than 22,000 mg of pembrolizumab (112 fixed doses) and more than 11,000 mg of nivolumab (47 fixed doses) were saved under this scheme.
Hall said the analysis strongly supported the idea of weight-based dosing.
“Finding ways to minimize drug wastage will be an important part of changing from fixed dosing to weight-based dosing,” he said. “We did take that into account and found that we still saved money even if we didn’t allow vials to be shared between patients. However, when we did allow the sharing of vials, that enhanced the savings even more, particularly for pembrolizumab.”
Hall added that he is hopeful that his findings may cause clinicians to rethink the ways these drugs are dosed.
“We believe the implementation of this on a large scale could result in a huge reduction in drug expenditure,” Hall told HemOnc Today. “Many oncologists may not feel that there is a big difference between weight-based and fixed-dosing of these drugs. I hope that showing that there’s a real economic impact without any anticipated clinical impact will cause this strategy to gain some traction.” – by Jennifer Byrne
Reference:
Hall ET, et al. Abstract 6504. Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.
Disclosures: Hall reports research to his institution from Noona Healthcare and a relationship with Cancer Support Community. Please see the abstract for all other authors’ relevant financial disclosures.