The safety of extended dosing pembrolizumab when compared to traditional dosing: A review and meta-analysis of retrospective studies.

BACKGROUND

To minimise healthcare exposure in the COVID 19 era, 6-weekly extended dosing pembrolizumab became widely accepted as an alternative to 3-weekly dosing based on modelling studies. A review and meta-analysis were performed to assess the real-world safety of 6-weekly pembrolizumab in relation to 3-weekly dosing.

METHODS

Following PRISMA guidelines, we conducted a meta-analysis encompassing retrospective studies of solid organ malignancies comparing 6-weekly pembrolizumab with 3-weekly pembrolizumab including patients switched to 6-weekly from 3-weekly pembrolizumab ("switched"). Primary outcomes were relative risk estimates (RR) of grade 3-5 immune related adverse events (irAEs) for 6-weekly and "switched" pembrolizumab in relation to 3-weekly dosing. Secondary outcomes were pooled proportions of grade 3-5 irAEs for 6-weekly, 3-weekly and "switched" patients. A random effects logistic regression was used to estimate RR and the results were depicted in forest plots.

RESULTS

10 studies were included with a total of 592 3-weekly, 520 6-weekly and 273 "switched" patients. 6-weekly pembrolizumab was not associated with increased rates of grade 3-5 irAEs when compared to 3-weekly dosing (RR 1.16; CI 0.85-1.58, p = 0.35). "Switched" 6-weekly patients had no significant difference in rates of grade 3-5 irAEs when compared to 3-weekly patients (RR 1.30; CI 0.87-2.07, p = 0.28). Total grade 3-5 irAEs for 6-weekly, 3-weekly and "switched" pembrolizumab patients were 15 %, 13 % and 16 %, respectively.

CONCLUSION

6-weekly pembrolizumab is not associated with increased grade 3-5 irAEs compared to 3-weekly pembrolizumab. Switching patients to 6-weekly pembrolizumab from 3-weekly dosing was not associated with an increased risk of grade 3-5 irAEs.