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Review
. 2024 Aug:200:104420.
doi: 10.1016/j.critrevonc.2024.104420. Epub 2024 Jun 19.

The spectrum of cutaneous toxicities related to novel genitourinary cancer therapies

Affiliations
Review

The spectrum of cutaneous toxicities related to novel genitourinary cancer therapies

Rachel Daher et al. Crit Rev Oncol Hematol. 2024 Aug.

Abstract

Context: Genitourinary cancers (GUCs) encompass malignancies affecting the urinary and reproductive systems, including renal cell carcinoma (RCC), urothelial carcinoma (UC), and prostate cancer (PC). With the rapidly evolving therapeutic domain of these cancers, cutaneous adverse events (AEs) remain among the most observed toxicities.

Objective: To explore the dermatologic AEs linked to novel GUC treatments, their underlying pathophysiology, clinical presentations, and risk factors.

Evidence acquisition: A narrative review of the literature from PubMed and Embase databases was conducted. The search strategy included dermatologic/cutaneous adverse events, risk factors, and pathophysiology in conjunction with the following classes of therapies; immune checkpoint inhibitors (ICIs), antiangiogenic therapies, enfortumab vedotin (EV), erdafitinib, and androgen receptor antagonists (ARAs).

Evidence synthesis: Maculopapular rash, pruritus, and alopecia are present among the five classes of therapies. ICIs demonstrate the highest incidence of severe drug AEs including Steven Johnson syndrome/toxic epidermal necrolysis. Unique cutaneous AEs present with specific therapies including hand-foot skin reaction and subungual splinter hemorrhage with antiangiogenic drugs, stomatitis/mucositis and onycholysis with erdafitinib. Incidence and type of cutaneous AE also differed within therapies in the same class as seen with apalutamide displaying the highest risk of cutaneous AEs within ARAs. Risk factors for development of cutaneous AEs can be general to therapies, or specific, and include age, immune status, BMI, and gender.

Conclusions: Dermatologic AEs may impact patients' quality of life and increase the tendency to dose reduce, hold or discontinue life-saving therapies, underscoring the need for vigilant monitoring, early recognition, and collaborative management between medical oncologists, pharmacists, dermatologists and other specialists.

Keywords: Cutaneous Adverse Events; Dermatology; Genitourinary Cancer; Oncology.

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Conflict of interest statement

Declaration of Competing Interest P. Grivas (last 3 years):Consulting: 4D Pharma, Aadi Bioscience, Asieris Pharmaceuticals, Astellas, AstraZeneca, BostonGene, Bristol Myers Squibb, CG Oncology, Dyania Health, Exelixis, Fresenius Kabi, G1 Therapeutics, Genentech, Gilead Sciences, Guardant Health, ImmunityBio, Infinity Pharmaceuticals, Janssen, Lucence, Merck KGaA, Mirati Therapeutics, MSD, Pfizer, PureTech, QED Therapeutics, Regeneron, Roche, Seattle Genetics, Silverback Therapeutics, Strata Oncology, UroGen Pharma. Research funding to institution: ALX Oncology, Acrivon Therapeutics, Bavarian Nordic, Bristol Myers Squibb, Clovis Oncology, Debiopharm Group, G1 Therapeutics, Gilead Sciences, GSK, Merck KGaA, Mirati Therapeutics, MSD, Pfizer, QED Therapeutics. P. Spiess: Vice chair of the National Comprehensive Cancer Center bladder and penile cancer panel. A. Kamat: Consulting/Advisory role: Astellas Pharma, Biological Dynamics, Bristol-Myers Squibb. CG Oncology, Cystotech, Eisai, EnGene, Ferring, Imagin Medical, Imvax, Incyte, Janssen, Medac, Merck, Nonagen Bioscience, Pfizer, Photocure, Protara Therapeutics, Roche, Seagen, Sessen Bio, Theralase, Urogen Pharma, US Biotest, Vivet Therapeutics. Research Funding: FKD Therapies (now Ferring), Patient-Centered Outcomes Research Institute (PCORI), Photocure, Seagen, EnGene, Arquer Diagnostics, SWOG. Patents: CyPRIT (Cytokine Predictors of Response to Intravesical Therapy) - Joint patent with MD Anderson Cancer Center. Leadership and Other Relationships: European Urology Oncology, International Bladder Cancer Group (IBCG), International Bladder Cancer Network (IBCN), Journal of Urology, UroToday. S. Gupta: Consulting fees: Bristol Myers Squibb, Merck, Bayer, Pfizer, EMD Sorono, Seattle Genetics, Gilead Sciences, Foundation Medicine, Guardant, and Astellas; Speaker bureau for Seattle Genetics, Bristol Myers Squibb and Gilead Sciences. Research grant/funding (institution) from Bristol Myers Squibb, Roche, Merck, Seattle Genetics, QED, Novartis, Moderna, EMD Sorono, and Pfizer; and is a shareholder of Moderna, Nektar Therapeutics and BioNTech. A. Necchi: Consulting/Advisory role: MSD, Roche, Bayer, AstraZeneca, Clovis Oncology, Janssen, Incyte, Seattle Genetics/Astellas, Bristol-Myers Squibb, Rainier Therapeutics, Bycicle Therapeutics, GlaxoSmithKline, Basilea Pharmaceutica, Catalym. Research Funding (Institution): MSD, AstraZeneca, Ipsen, Gilead. Honoraria: Roche, MSD, AstraZeneca, Janssen, Foundation Medicine, BMS, Astellas. Travel, Accommodations, Expenses: Roche, MSD, AstraZeneca, Janssen, Rainer Therapeutics, Pfizer. Employment and Stock Ownership(spouse): Bayer. Academic Appointments: Vice-president of the Global Society of Rare GU Tumors (GSRGT), ESMO 2024 Annual Meeting Planning Committee – GU Kidney and Bladder cancers track, ESMO Faculty–Genitourinary tumors-Non prostate, 2021–2025, Panel member of the ASCO/EAU penile cancer guidelines committee, Board member – EAU Research Foundation (EAU-RF).

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