Personalized Dosing Versus Fixed Dosing of Immune Checkpoint Inhibitors: A Cost Analysis Study.

To the Editor: In 2016, the Food and Drug Administration modified the dosage regimen for nivolumab to a flat dose of 240 mg based on a pharmacokinetic analysis.1 Similarly, a flat dose of 200 mg of pembrolizumab was approved by the Food and Drug Administration to treat non–small-cell lung cancer based on the results of the KEYNOTE 024 study.2 Evidence suggests that pembrolizumab has equivalent efficacy whether a dose of 2 or 10 mg/kg is used.3 Recently, Goldstein et al4 have demonstrated that a flat dose of pembrolizumab over the standard weight-based regimen in first-line metastatic non– small-cell lung cancer leads to a significant financial burden. We performed a study to investigate whether a flat dose of nivolumab or pembrolizumab is associated with increased immune-related toxicity or financial burden compared with regular weight-based regimens. Our secondary objective was to assess whether the clinical efficacy differs between these 2 dosing regimens, as measured by overall survival. Our final analysis included 137 patients who were treated with nivolumab or pembrolizumab at the University of Oklahoma Health Sciences Center between 2014 and 2018. Patients who received both flat and weight-based dose of either agent were excluded from the analysis. Simple descriptive statistics were created for all covariates. Chi-square analysis was performed to compare the immune-related adverse events between the 2 groups. We calculated Kaplan–Meier survival curves, followed by a logrank test to compare survival. We then used Cox proportional hazards model to adjust for possible confounding variables. Finally, to determine the financial burden of these agents, we looked at the total dose received by patients treated with a flat dose and calculated the dose they would have received based on their weight (2 mg/kg for pembrolizumab and 3 mg/kg for nivolumab) to analyze the cost difference. The median age of patients was 61 years, and females comprised 53% of the study population. The median body weight and body mass index were 73 kg and 25 kg/m2, respectively. Lung cancer was the most common diagnosis (25%), followed by melanoma (20%). Pembrolizumab (50%) and nivolumab (50%) were used in a similar frequency. Most patients received a flat-dose treatment (64%). After adjustment for age, performance status, body mass index, cancer type, and line of treatment, there was no difference in overall survival by the dose type (P 5 0.28). The incidence of immune-related adverse events was similar across dose types after adjusting for age, body weight, performance status, cancer type, agent used, and line of therapy (P 5 0.08). Patients treated with flat-dose pembrolizumab received on average a total of 50.6 mg more per dose than they would have received with the weight-based dose (n 5 60) and those treated with flat-dose nivolumab received 3.4 mg less per dose (n 5 25). Average sales prices from the first quarter of 2015 show the average per-mg wholesale prices to be $28.78 for nivolumab and $51.79 for pembrolizumab. Taking this into consideration, we estimated that personalized dosing of these 2 drugs would have saved $1820.46 (Std dev $2606.91) per patient per course of treatment leading to a total savings of $642,877 over all courses of therapy. Using our single-institution database, we found evidence that the conventional weight-based regimen of immune checkpoint inhibitors could potentially be beneficial from a financial standpoint without compromising the clinical outcomes.