Comparison of pembrolizumab dosing regimens and incidence and severity of immune-related adverse effects: A retrospective, case-control study.

[PURPOSE] To evaluate the differences in the incidence and severity of immune-related adverse effects (irAEs) between the pembrolizumab 21-day dosing schedule and the 42-day dosing schedule.

[METHODS] Patients with solid tumor malignances and no previous immunotherapy exposure were included. This case-control study compared patients on pembrolizumab 200 mg every 21 days with those on 400 mg every 42 days in a 2:1 ratio. The primary outcome was the rate of all grades of irAEs.

[RESULTS] A total of 160 patients who received treatment every 21 days and 80 patients who received treatment every 42 days were evaluated. All-grade irAEs occurred in 33.1% (53/160) and 32.5% (26/80) of patients in the 21-day group and the 42-day group, respectively. Regarding severe irAEs (grade 3 or worse), these occurred in 32.1% (17/53) and 23.1% (6/26) of patients in the 21-day and 42-day cohorts, respectively (P = 0.444). Additionally, no significant association was found between dosing schedule and steroid initiation (P = 0.595) or treatment discontinuation (P = 0.192).

[CONCLUSION] The comparison of the 21-day and 42-day pembrolizumab dosing cohorts revealed similar irAE rates and severity of toxicities. Rates of steroid initiation for irAE management and permanent treatment discontinuation due to irAE did not significantly differ between dosing schedules. While severe irAEs correlated with treatment discontinuation, dosing schedule did not differentially affect this outcome. Overall, extending the pembrolizumab dosing interval to 42 days appears safe while maintaining an irAE profile comparable to that with the standard 21-day schedule.