Abstract
Introduction: Extended-interval dosing (ED) for immune checkpoints inhibitors (ICI) anti-PD-1 (nivolumab, pembrolizumab) or anti-PD-L1 (durvalumab) were approved based on population pharmacokinetic analyses that predicted a benefit–risk profile comparable to the standard dosing (SD) regimen. Since safety data in real-world conditions of use are lacking, the aim of this study was to compare the incidence and the risk factors of immune related adverse events (irAEs) between SD and ED regimen.Material and methods: We conducted a retrospective observational study across two oncology centers. The incidence of irAES in medical records of patients receiving either SD or ED regimen of ICI between January 1, 2019, and December 31, 2020, were analyzed using Cox regression model with time-dependent covariates.Results: Among 957 patients treated with anti-PD-1/PD-L1 during the data collection period, 686 patients were included: 430 new users of a SD regimen, 161 patients who started with SD and switched to ED regimen during follow-up, and 95 new users of an ED regimen. Overall, 377 irAEs were reported for 237 patients: 34.6% experienced at least one irAE of any grade and 11.4% presented at least one grade ≥ 3 irAE. No statistically significant difference was observed 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 (adjusted HR 1.67, 95%CI: 0.78–3.55). Pre-existing auto-immune condition was confirmed to be a risk factor of irAEs (HR 2.23, 95%CI: 1.35–3.70). Concurrent use of an immunosuppressive drug, radiotherapy or targeted therapy was not associated with an increased incidence of irAEs. Interestingly, in a secondary analysis, renal carcinoma appears to be associated with grade ≥ 3 irAEs (OR 6.35; 95%CI: 1.69–23.89).Discussion/Conclusion: These results suggest that ICI safety is not correlated to the dosing schedule. This has to be confirmed with ongoing clinical studies.