Revisiting the association between skin toxicity and better response in advanced cancer patients treated with immune che
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Journal of Translational Medicine Open Access
RESEARCH
Revisiting the association between skin toxicity and better response in advanced cancer patients treated with immune checkpoint inhibitors Nicholas Gulati1† , Douglas Donnelly1†, Yingzhi Qian2, Una Moran1, Paul Johannet1, Judy Zhong2 and Iman Osman1*
Abstract Background: Immune checkpoint inhibition (ICI) improves survival outcomes for patients with several types of cancer including metastatic melanoma (MM), but serious immune-related adverse events requiring intervention with immunosuppressive medications occur in a subset of patients. Skin toxicity (ST) has been reported to be associated with better response to ICI. However, understudied factors, such as ST severity and potential survivor bias, may influence the strength of these observed associations. Methods: To examine the potential confounding impact of such variables, we analyzed advanced cancer patients enrolled prospectively in a clinicopathological database with protocol-driven follow up and treated with ICI. We tested the associations between developing ST, stratified as no (n = 617), mild (n = 191), and severe (n = 63), and progression-free survival (PFS) and overall survival (OS) in univariable and multivariable analyses. We defined severe ST as a skin event that required treatment with systemic corticosteroids. To account for the possibility of longer survival associating with adverse events instead of the reverse, we treated ST as a time-dependent covariate in an adjusted model. Results: Both mild and severe ST were significantly associated with improved PFS and OS (all P
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