Diverse landscape of dermatologic toxicities from small‐molecule inhibitor cancer therapy

Abstract

Background: Advances in molecular biology and genetics have contributed to breakthrough treatments directed at specific pathways associated with the development of cancer. Small-molecule inhibitors (Nibs) aimed at a variety of cellular pathways have been efficacious; however, they are associated with significant dermatologic toxicities. Methods: We conducted a comprehensive review of dermatologic toxicities associated with Nibs categorized into the following five groups: (a) mitogen-activated protein kinase; (b) growth factor/multi-tyrosine kinase; (c) cell division/DNA repair; (d) signaling associated with myeloproliferative neoplasms; and (e) other signaling pathways. Prospective phase I, II, or III clinical trials, retrospective literature reviews, systematic reviews/meta-analyses, and case reviews/reports were included for analysis.Results: Dermatologic toxicities reviewed were associated with every class of Nibs and ranged from mild to severe or life-threatening adverse skin reactions.Inflammatory reactions manifesting as maculopapular, papulopustular/acneiform, and eczematous lesions were frequent types of dermatologic toxicities seen with Nibs.Squamous cell carcinoma with keratoacanthoma-like features was associated with a subset of Nibs. Substantial overlap in dermatologic toxicities was found between Nibs.Conclusions: Dermatologic toxicities from Nibs are diverse and may overlap between classes of Nibs. Recognition of the various types of toxicities from Nibs is critical for patient care in the era of "oncodermatology/dermatopathology."

The diverse landscape of dermatologic toxicities of non‐immune checkpoint inhibitor monoclonal antibody‐based cancer therapy

“…This review aims to be the most comprehensive catalog of the dermatologic toxicity profile of non‐ICI mAb‐based cancer therapies. Compared with those associated with ICIs and Nibs, 12,13,45 we found that the dermatologic toxicities with these non‐ICI mAbs are mostly inflammatory and not typically characterized by histopathologic evaluation (Tables 2 and 3). Inflammatory reactions to mogamulizumab have the most comprehensive histopathologic description among the non‐ICI mAbs and include lichenoid/interface, psoriasiform, spongiotic, and granulomatous morphology and may rarely exhibit vitiligo‐like reactions 125,128–131,188,290 .…”

“…The emergence of the fields of oncodermatology and oncodermatopathology have led to enhanced awareness of the mucocutaneous reactions associated with cancer therapy and their impact on patients' quality of life 11 . We previously reviewed the dermatologic toxicities associated with cancer therapy using small‐molecule inhibitors (Nibs) or immune checkpoint inhibitors (ICIs), categorizing these toxicities as inflammatory, immunobullous, alterations of epidermal keratinocytes, alterations of epidermal melanocytes, or cutaneous deposits 12,13 . In this review, we provide a comprehensive catalog of dermatologic toxicities associated with non‐ICI mAbs, with particular attention to their histopathologic features.…”

“…11 We previously reviewed the dermatologic toxicities associated with cancer therapy using small-molecule inhibitors (Nibs) or immune checkpoint inhibitors (ICIs), categorizing these toxicities as inflammatory, immunobullous, alterations of epidermal keratinocytes, alterations of epidermal melanocytes, or cutaneous deposits. 12,13 In this review, we provide a comprehensive catalog of dermatologic toxicities associated with non-ICI mAbs, with particular attention to their histopathologic features. These non-ICI mAbs are categorized into two groups based on their approval for treating (1) solid tumors and…”

Bosutinib-Induced Stevens-Johnson Syndrome and Evidence of Tolerance to a Structurally Dissimilar Tyrosine Kinase Inhibitor

“…In patients with delayed cutaneous hypersensitivity drug reactions to imatinib and dasatinib, patch tests at 1%, 5%, and 10% have been used in previous studies [ 9 ]. Small inhibitor molecule therapy with agents similar to TKIs can cause a vast array of dermatologic toxicities, ranging from simple maculopapular rashes to severe reactions such as SCARs [ 10 ].…”

Gene expression profiling and multiplex immunofluorescence analysis of bullous pemphigoid immune‐related adverse event reveal upregulation of toll‐like receptor 4/complement‐induced innate immune response and increased density of TH1 T‐cells

“…1 They occur in fewer than 1% of patients treated with targeted inhibitors of BRAF and other small-molecular inhibitors. 1,2 Bullous pemphigoid (BP)-irAE is the most commonly reported autoimmune blistering process among cancer patients treated with anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) therapies. 3,4 A review of 58 cases of BP-irAE associated with anti-PD-1/PD-L1 immunotherapy demonstrated a median latency of $28 weeks and most often clinical presentation as an eczematous or urticarial lesion or blisters (80%) with a histopathologic pattern of subepidermal bullae (71%) and eosinophils (81%).…”