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Page 741 Giuliani et al. Cancer Drug Resist 2021;4:740-4 https://dx.doi.org/10.20517/cdr.2021.14

Table 1. Cost of drugs
Drug Pharmacy cost (€) (dose)
Gemcitabine 9.90 (1000 mg)
Paclitaxel 6.19 (100 mg)
Docetaxel 9.84 (80 mg)
Carboplatin 7.18 (150 mg)
Cisplatin 8.80 (50 mg)
Vinorelbine 6.54 (10 mg)
Nab-paclitaxel 214.48 (100 mg)
Bevacizumab 2004.61 (1 administration at 7.5 mg pro Kg)
2672.28 (1 administration at 15.0 mg pro Kg)
Pemetrexed 226.65 (100 mg)
Pembrolizumab 2056.08 (100 mg)
Erlotinib 45.80 (150 mg tablet)
Gefitinib 72.06 (250 mg tablet)
Afatinib 65.85 (20 mg tablet)
Osimertinib 145.28 (80 mg tablet)

The aim of our study was to assess the pharmacological costs of TKIs (erlotinib, gefitinib, afatinib and
osimertinib) in patients with activating EGFR mutations in first-line treatment for advanced NSCLC.
Pivotal phase III randomized controlled trials (RCTs) were considered. The last available update of each
trial was considered as the original source. The deadline for trial publication and/or presentation was 30
June 2020. Incremental cost-effectiveness ratio (ICER) was calculated as the ratio between the difference of
the costs in the intervention and in the control groups (pharmacy costs) and the difference between the
effect in the intervention and in the control groups [overall survival (OS)]. The costs of drugs were based on
those at the pharmacy of our hospital and are expressed in euros (€), updated to June 2020. The pharmacy
costs of drugs are summarized on Table 1. The dosages of drugs were considered according to those
reported in each RCT. The European Society for Medical Oncology Magnitude of Clinical Benefit Scale
(ESMO-MCBS) was applied the to the pivotal RCTs to derive a relative ranking of clinical benefit . All
[4]
[5]
data were reviewed by two investigators (Giuliani J and Bonetti A) and separately computed by two
investigators (Giuliani J and Bonetti A).
Nine phase III RCTs [6-14] , including 2291 patients, were considered. The OS of TKIs ranged from 18.8
months for gefitinib in the IPASS trial [8,15] to 38.6 months in the FLAURA trial [14,16] . ESMO-MCBS reached
Grade 4 for OPTIMAL trial , EURTAC trial , IPASS trial , LUX-Lung 3 trial and FLAURA trial ;
[6]
[8]
[12]
[14]
[7]
[13]
[10]
[9]
[11]
Grade 3 for NEJ2002 trial , WJTOG3405 trial and LUX-Lung 6 ; and Grade 1 for First-SIGNAL trial .
The lowest cost for 1 month of OS gain was associated with osimertinib, at €9740 per month OS gained
[Table 2].
Two main variables influence pharmacy costs: the efficacy of treatment and the price of drugs. The first
variable is related to the patient’s inclusions criteria, and we know that results from RCTs might not be
representative of daily clinical practice (i.e., of patients treated outside such trials). The price of drugs is the
second strong variable. In fact, there may be a cost standardization problem within different European
countries (in Italy, there are no significant pharmacy cost differences among the different regions), due to
the use of local pharmacy cost. Another limit is related to the consideration of only direct costs (which
account for about 55% of total medical expenses). In Europe, expenditure for cancer drugs amounted to €10
billion in 2005, increasing more than three times to €32 billion in 2018 . In this scenario, European
[17]
countries negotiate the price of new drugs with the manufacturers with the aim to obtain a discount, so as to