Résumé
Background: extended-interval dosing (ED) for inhibitors of programmed cell death protein 1 (anti-PD-1) (Nivolumab, pembrolizumab) or its ligand (anti-PD-L1) (durvalumab) were recently approved by European Medicines Agency (EMA) based on pharmacokinetic model simulation results that predicted a comparable benefit-risk profile than the standard dosing (SD) regimen. However, safety data in real-world condition of use are lacking.Objective: to compare the incidence of serious immune related adverse events (irAEs) and any grade irAEs between SD and ED regimen in patients treated with an anti-PD-1 or anti-PD-L1.Methods: we retrospectively assessed irAEs from medical records in all new users of Nivolumab, pembrolizumab or durvalumab from January 1, 2019 to December 31, 2020 across two oncology centers in France. Immune checkpoint inhibitors (ICI) were administered as SD or ED regimen. We used Cox proportional hazards models to compare the incidence of irAEs between both dosing regimens, adjusting for the main available confounders.Results: among the 686 patients included, we identified 430 new users of a SD regimen only, 161 patients who started with SD and switched to ED regimen during follow-up, and 95 new users of an ED regimen only. Overall, 377 irAEs were reported among 237 patients: 34.6% experienced at least one irAE of any grade and 11.4% presented at least one serious grade ≥3 irAE. There was no statistically significant difference when comparing SD regimen versus ED regimen on the risk of grade ≥3 irAEs (adjusted HR 0.79, 95% CI: 0.30-1.04) as well as on the risk of any grade irAEs (adjusted HR 1.67, 95% CI: 0.78-3.55). IrAEs resolved without sequelae in 46.4% of cases, 0.8% (n=3) were fatal. Renal cell cancer or urinary carcinoma were considered as a new risk factor for all grade irAEs (HR=2.27; 95% CI: 0.97-5.34) and for grade ≥3 irAEs (HR 3.90; 95% CI: 1.39-10.90).Conclusions: in a real-world setting, we did not observe an increase in irAE incidence between SD versus ED regimen. This study suggests that ICI safety is not correlated to the chosen dosing schedule. Consequently, the choice of the best dosing regimen belongs to the oncologist, taking into account the patient’s general condition.