Pharmacovigilance analysis found significant signals between PD-1/PDL-1 inhibitors and keratoacanthomas as well as cutaneous squamous cell carcinoma, although this finding can not be used to establish causality.
Clinical Pearls
This database analysis aimed to determine if any associations existed between PD-1 or PDL-1 inhibitors and keratoacanthomas or cutaneous squamous cell carcinoma using the FDA’s Adverse Events Reporting System
Of the 158,000 reports of PD-1/PDL-1 inhibitor use, there were 43 patients who developed keratoacanthomas and 83 who developed cutaneous squamous cell carcinoma
Pharmacovigilance analysis found significant signals between PD-1/PDL-1 inhibitors and keratoacanthomas as well as cutaneous squamous cell carcinoma, although this finding can not be used to establish causality.
Discussion:
In this research letter published in JAMA Dermatology, Aggarwal and colleagues aimed to investigate if use of PD-1/PDL-1 inhibitors is associated with development of keratoacanthoma or cutaneous squamous cell carcinoma (cSCC). Using the Federal Drug Administration (FDA) – Adverse Event Reporting System (FAERS), the authors searched for all reported developments of keratoacanthoma or cSCC in PD-1/PDL-1 treated patients. Importantly, the authors performed pharmacovigilance identification via disproportionality analysis, not allowing one to establish causality from their results.
Among 158,000 patients found using or having had used PD-1/PDL-1 inhibitors, 43 patients developed keratoacanthomas and 83 developed cSCC. Although the authors were limited by less data on withdrawal of PD-1/PDL-1, they were able to find that in 10 reports of PD1/PDL-1 associated keratoacanthoma, all 10 keratoacanthomas resolved after discontinuation or dose reduction. Additionally, in 17 reports of PD-1/PDL-1 associated cSCC, 10 cSCC’s resolved after discontinuation or dose reduction. Interestingly, there was one report of keratoacanthoma development following readministration of a PD1/PDL-1 inhibitor.
Overall, this data is valuable in that it shows how PD1/PDL-1 inhibitors may be associated with development of these cutaneous tumors. However, readers should keep in mind this study does not establish a causal relationship between the two and larger scale studies are required.
Comments