Trends in Spontaneous Adverse Event Reports Following the Expansion of Pembrolizumab Indications in Japan

Pembrolizumab is an immune checkpoint inhibitor that has been widely used in cancer treatment, and its approved indications have expanded rapidly in recent years. However, the effects of this increase on immune-related adverse events (irAEs) remain unclear. Using data from the Japanese Adverse Drug Event Report (JADER) database and the National Database of Health Insurance Claims and Specific Health Checkups (NDB Open Data), we analyzed trends in the number and characteristics of spontaneously reported adverse events associated with pembrolizumab from fiscal years 2016 to 2024. The number of adverse event reports in JADER generally increased in parallel with prescription volume. Following the expansion of indications for gynecological cancers (such as breast, uterus, and cervix cancers) around 2021, a marked increase in reports was observed from 2022. During this period, the demographic profile of reported patients shifted from predominantly older males to middle-aged females. Regarding cancer types, the proportion of reports on breast and uterus cancers increased significantly, whereas those on lung cancer declined. In addition to pulmonary disorders, endocrine disorders became increasingly reported and represented the most frequent category in fiscal year 2022. The distribution of irAEs by cancer type suggested potential associations; pulmonary toxicity was more frequent in lung cancer, whereas endocrine toxicity was predominant in breast, uterus, and cervix cancers. Our findings indicate that the expansion of pembrolizumab indications has substantially altered the profile of reported immune-related adverse events in Japan, highlighting the need for ongoing pharmacovigilance tailored to cancer type and patient demographics.