Background In Italy, on 2 May 2018, the use of nivolumab (Obdivo) was approved in monotherapy in a 240 mg dose every 2 weeks to replace the weight-based dosage (3 mg/kg) for all approved indications (melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC)) and a dose of 480 mg every 4 weeks (melanoma and RCC). The dosage change was based on pharmacokinetic data that showed good safety up to a dose of 10 mg/kg. The previous dosage was defined as off-label.

Purpose The purpose of this study was to evaluate any change in the drug-related adverse (ADR) events and any additional costs after the transition to the flat dose.

Material and methods We collected data from the National Pharmacovigilance Network (NPN) from the 2 May to 15 October in the years 2016, 2017 and 2018. The number of reported ADRs and the percentage of severe ADR has been compared (deaths were not considered). For the estimation of costs we considered all patients who received nivolumab treatment from 2016. For the naive patients after the 2 May, the dose was calculated with the old scheme of 3 mg/kg. For patients who had already discontinued therapy, the dose difference was calculated with the flat dose. The price ex-factory per mg was €13.44.

Results The reported ADRs in NPN were, respectively: 174 (35.1% serious), 192 (34.4% serious) and 175 (58.3% serious). For the estimation of costs, an average increase of 35.3 mg for a single administration, corresponding to an increase of €474.43, was measured.

Conclusion Since the flat dose was calculated on a hypothetical patient weighing 80 kg, it was easy to view a rapid increase in direct costs related to the drug (11 out of 15 of the patients considered had lower weight). Despite the bias related to the applied methodology, it is possible to think that the costs associated with nivolumab will increase. Furthermore, it is not clear why the 3 mg/kg dosage is to be considered off-label. Furthermore, it is interesting to note that the number of serious ADRs has increased. However, pharmacovigilance monitoring is required to evaluate changes in the safety profile.

References and/or acknowledgements No conflict of interest.