Sex- and Cancer-Related Differences in Reported Adverse Reactions with Pembrolizumab Monotherapy: A Real-World Pharmacovigilance Analysis from EudraVigilance

Background/Objectives: Sex-related differences in reporting of adverse reactions to pembrolizumab remain incompletely characterized across tumour types. We investigated the associations of sex, age, and tumour histotype with organ-specific reporting patterns and adverse-reaction reporting multiplicity in EudraVigilance. Methods: We retrospectively analysed individual case safety reports (ICSRs) involving pembrolizumab monotherapy from 1 January to 31 December 2025. Suspected adverse drug reactions (ADRs) were grouped by MedDRA System Organ Class (SOC); reporting multiplicity was defined as one versus at least two ADRs per ICSR. Associations were examined using chi-square tests and Cramér’s V, with Bonferroni correction across nine SOCs and multivariable logistic regression adjusted for age and tumour histotype. Results: Among 8488 eligible ICSRs, sex was recorded in 7991, age in 6941, and tumour type was evaluable in 6482 reports across 14 categories. Reporting multiplicity did not differ by sex (p = 0.110). In unadjusted analyses, women had higher reporting proportions of endocrine (18.4% vs. 12.4%) and blood and lymphatic disorders (13.4% vs. 9.5%), whereas men had higher proportions of respiratory (12.4% vs. 7.0%) and cardiac disorders (13.9% vs. 11.5%); all four associations met the Bonferroni threshold. None remained significant after adjustment for age and tumour histotype. Reporting multiplicity differed modestly by age (p = 0.026) and by tumour type (p = 0.016), with small effect sizes. Conclusions: Sex-related organ-specific differences in spontaneous reporting may partly reflect tumour-type composition rather than independent sex effects. These hypothesis-generating signals require confirmation in prospective studies with treatment-exposure denominators.