Safety of Extended interval Dosing Immune Checkpoint Inhibitors: a multicentre cohort study

Background: Real-life spectrum and survival implications of immune-related adverse events (irAEs) in patients treated with extended interval dosing (ED) immune checkpoint inhibitors (ICIs) are unknown. Methods: Characteristics of 812 consecutive solid cancer patients who received at least one cycle of ED monotherapy (pembrolizumab 400 mg Q6W or nivolumab 480 mg Q4W) after switching from canonical interval dosing (CD, pembrolizumab 200 mg Q3W or nivolumab 240 mg Q2W) or upfront were retrieved. Primary objective was to compare irAEs patterns within the same population (before and after switch to ED). irAEs spectrum in patients treated upfront with ED and association between irAEs and overall survival (OS) were also described. Results: 550 (68%) patients started ICIs with CD and switched to ED. During CD, 225 pts (41%) developed any grade and 17 (3%) G3/G4 irAEs; after switching to ED, any grade and G3/G4 irAEs were experienced by 155 (36%) and 20 (5%) patients. Switching to ED was associated with a lower probability of any grade irAEs (adjusted odds ratio [aOR]: 0.83; 95% CI: 0.64-0.99; p=.047), while no difference for G3/G4 events was noted (aOR: 1.55; 95% CI: 0.81-2.94; p=.18). Among patients who started upfront with ED (n = 232, 32%), 107 (41%) developed any grade and 14 (5%) G3/G4 irAEs during ED. Patients with irAEs during ED had improved OS (aHR: 0.53; 95% CI 0.34-0.82; p=.004 after switching; aHR: 0.57; 95% CI 0.35-0.93; p=.025 upfront). Conclusions: Switching ICI treatment from CD and ED did not increase the incidence of irAEs and represents a safe option also outside clinical trials.