Reply to the letter to the editor ‘Response to the effect of PD-L1 testing on the cost-effectiveness of immune checkpoint inhibitors’ by Ogale
Authors: G. de Lima Lopes, P. Aguiar
Journal: Annals of Oncology (2018)

Thank you for the opportunity to reply to the comment [1.Ogale S. Response to ‘The effect of PD-L1 testing on the cost-effectiveness of immune checkpoint inhibitors.Ann Oncol. 2018; 29: 21-40Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar] on our article [2.Aguiar Jr., P.N. Perry L.A. Penny-Dimri J. et al.The effect of PD-L1 testing on the cost-effectiveness and economic impact of immune checkpoint inhibitors for the second-line treatment of NSCLC.Ann Oncol. 2017; 28: 2256-2263Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar]. It gives us the prospect of dispelling a common misunderstanding readers have about our article. We did not aim to compare anti-programmed cell death (PD)-1 and PD-L1 agents against one another; our primary aim was to compare each checkpoint inhibitor against itself with and without the use of PD-L1 expression as a predictive biomarker. As such, it is important that the reader understand that any comparisons across these drugs are beyond the scope of our methodology and our study should not be used to determine whether any of these medications is more cost-effective than the others. Having said that, we do have to strongly disagree with several points made in the commentary. First, there are no errors in our calculations or in assumptions. When doing health technology assessments and cost-utility studies, one has to make assumptions when developing a model. These are inherent to the methods and we clearly state these in our article. Moreover, we made every attempt to stay as close to the data available and to make as conservative an estimate as possible. The costs considered for each drug were the costs publically available in November 2016. Drugs costs are difficult to standardize due to stealthy trading and commercial strategies of manufacturers and payers. Moreover, we did not consider using a flat dose of nivolumab and pembrolizumab because we strictly followed the doses used in the randomized clinical trials from which we extracted all clinical data. In addition, we considered that there is overspending driven by oversized single-dose vials of cancer drugs as reported previously by Bach et al. [3.Bach P.B. Conti R.M. Muller R.J. et al.Overspending driven by oversized single dose vials of cancer drugs.BMJ. 2016; 352: i788Crossref PubMed Scopus (91) Google Scholar] and believed that payers and providers should have the opportunity of assessing cost-utility in such a way when the drug was studied on a per kilogram base in the appropriate clinical trial. Unfortunately a minority of centers in the United States use this approach today, increasing overall costs to the healthcare system. One also has to make it clear that atezolizumab is not the least expensive option, even when we consider all costs provided by Dr Ogale (as we can see in Table 1).Table 1Costs analysis considering values provided by Dr OgaleDrugDose studiedDrug price/mgSourcePrice/cycleMedian number of cyclesTotal priceNivolumab (Squamous)3 mg/kg Q2W$26.064CMS Limit (October 2016)$5473.4415$82 101.60Nivolumab (NSq)3 mg/kg Q2W$26.064CMS Limit (October 2016)$5473.4414$76 628.16Pembrolizumab2 mg/kg Q3W$46.495CMS Limit (October 2016)$6509.309$58 583.70Atezolizumab1200 mg Q2W$7.183WAC (October 2016)$8619.608$68 956.80Nivolumab (Squamous)3 mg/kg Q2W$27.155CMS Limit (July 2018)$5702.5515$85 538.25Nivolumab (NSq)3 mg/kg Q2W$27.155CMS Limit (July 2018)$5702.5514$79 835.70Pembrolizumab2 mg/kg Q3W$48.514CMS Limit (July 2018)$6791.969$61 127.64Atezolizumab1200 mg Q2W$7.6895CMS Limit (July 2018)$9227.408$73 819.20 Open table in a new tab Finally, our sensitivity analyses highlighted the significance of body weight variations in cost-effectiveness when flat doses are not used. This study was funded by authors (no grant is applicable).