A real-world study on the safety of the extended dosing schedule for nivolumab and pembrolizumab in patients with solid tumors.

Background: In addition to 2-weekly nivolumab 240 mg or 3-weekly pembrolizumab 200 mg, extended dosing intervals of 4-weekly nivolumab 480 mg or 6-weekly pembrolizumab 200 mg were approved. To date, the clinical safety of the extended dosing schedules of immune checkpoint inhibitors (ICIs) has not been adequately investigated in patients with solid tumors.

Methods: This real-world study enrolled patients with solid tumors who received nivolumab 480 mg every 4 weeks or pembrolizumab 400 mg every 6 weeks at the Kyoto Prefectural University of Medicine in Japan, between August 2020 and December 2021.

Results: Sixty-nine patients with solid tumors received an extended-interval dosing schedule during this period. Among them, 60 received it during treatment (cohort A), and nine received it for the first time (cohort B). After the extended dosing interval of ICIs in cohort A, 13 (21.7%) patients developed immune-related adverse events (irAEs). Seven of the 13 patients (53.8%) developed irAEs during the first cycle of the extended dosing interval. All patients who developed irAEs during the first cycle of the extended dosing interval had pre-existing antibodies. Multivariate analysis indicated that patients with pre-existing anti-thyroid antibodies had a significantly higher irAE incidence after starting extended dosing intervals (odds ratio: 6.41; 95% confidence interval: 1.46-28.2, p = 0.01).

Conclusions: Most patients were allowed to continue ICI therapy after an extended dosing interval. Patients with pre-existing antibodies, particularly anti-thyroid antibodies, may be prone to developing irAEs after starting extended dosing intervals and should be treated with caution.