Cutaneous Toxicity Research Articles

OTHR-37. Pediatrics Cutaneous Reactions in Patient Treated with the Mitogen-Activated Protein Kinase Extracellular Signal-Regulated Kinase Inhibitor Trametinib

OBJECTIVE: To describe the cutaneous adverse effects (AE) to MAPK Extracellular Signal-Regulated Kinase (MEK) Inhibitor Trametinib in the pediatric population. METHODS: This was a retrospective single-center study. Included were all pediatric patients, treated with trametinib, for an oncologic indication. All patients were evaluated by a pediatric dermatologist, prior to, and during treatment, with documentation of cutaneous findings. RESULT: Twenty patients were enrolled in the study. All patients received treatment with trametinib, of which 6 received a combination of trametinib and dabrafenib (BRAF inhibitor). Out of twenty patients, 18 patients (90%) presented with at least one cutaneous AE. Xerosis and pruritic eczematous changes were the most common (15 patients, 75%), which, in most cases, were tolerable and responded well to the use of emollients and topical corticosteroids. Eleven patients (55%) presented with paronychia which was treated with topical combined corticosteroids antifungals and antibiotics, all with good response. Six patients (30%) presented with acneiform eruption, treated with topical antibiotic, benzoyl peroxide and tretinoin, mostly with good response. Six patients (30%) presented with irreversible hair heterochromia. Reaction grades were reported for cutaneous reactions, most of them were Grade I or II. Only 2 patients reported to have grade III and IV cutaneous reactions: exfoliative dermatitis and erythema multiforme, respectively. Out of 6 patients that received combined treatment of trametinib and dabrafenib one patient had no cutaneous adverse reaction, and one had panniculitis (which was related to dabrafenib). The rest presented relatively mild AE. DISCUSSION: Cutaneous AEs are very common in children and adolescents treated with trametinib, and in most cases are classified as mild. Nevertheless, as this treatment is usually chronic, it is important to inform the patients and their guardians of the potential cutaneous toxicities prior to treatment initiation, and to refer them to a dermatologist for proper management.

Association of immune-related adverse events with immune-checkpoint inhibitors and treatment response in melanoma patients.

e21522 Background: Immune-related adverse effects (irAE´s) of immune-checkpoint inhibitors (ICIs) have been linked with a better treatment response in melanoma patients, especially cutaneous toxicities. However, little is known regarding other irAE´s which is important as they can be used as clinical markers of an adequate therapeutical response. Methods: We conducted a retrospective study on patients who were diagnosed with melanoma and received treatment with ICI´s between January 2015 until December 2021, immune related adverse events and their relationship with overall survival in melanoma patients treated with ICIs was the main objective of this study. Results: 53 records of patients with advance melanoma treated with ICIs between january 2016 to december 2021, demographic characteristics were as follow: 64.2% were male, mean age at diagnoses was 60.3 years, 41.5% had smoking history and 15.1% were Jewish. At diagnosis 73.6% of patients had a good functional status (ECOG 0-1). The most common histological subtypes were epithelioid (34%), and nodular (22.6%). Lung metastases was the most common affected site (49.1%), followed by brain 43.4% and non-regional nodes 42.5%. BRAF mutations was determined in 81.1% of the biopsies and 36% of them being V600E mutation. ICI´s was the preferred first line treatment in 83% of cases, median number of administered cycles were 6 (range 1-54 cycles), 60.4% of patients received pembrolizumab, 37.7% nivolumab plus ipilimumab, 20.8% nivolumab monotherapy and 5.7% ipilimumab. Throughout the studied period IrAE´s were reported in 34% of patients with 66.7% of them being grade 1-2 and 33.3% grade 3-4. The most common IrAE’s: vitiligo 38.8%, hypothyroidism22% and 3.8% pneumonitis. Median PFS at 12 months and OS was significantly better in the group of patients with irAE´s: Patients who develop an irAE´s are 7 times more likely to be disease free at 12 months and 4.1 times more likely to have a longer OS regardless of severity and type of toxicity. The impact of developing irAEs is significantly important for PFS (HR: 11.9, CI 95%: 3.28-4.71) as median PFS was not yet reached in this group. Conclusions: Development of irAEs is associated with favorable outcomes to ICIs with patients being 7 times more likely to be 12-month disease free and 4.1 times more likely to have a longer OS. irAEs can be used as clinical markers of an adequate treatment response.[Table: see text]

Decreased HMGB1 expression contributed to cutaneous toxicity caused by lapatinib

The application of lapatinib, a widely used dual inhibitor of human epidermal growth factor receptor 1 (EGFR/ERBB1) and 2 (HER2/ERBB2), has been seriously limited due to cutaneous toxicity. However, the specific mechanism of lapatinib-induced cutaneous toxicity has not been clarified, leading to the lack of an effective strategy to improve clinical safety. Here, we found that lapatinib could induce mitochondrial dysfunction, lead to DNA damage and ultimately cause apoptosis of keratinocytes. In addition, we found that lapatinib could induce an aberrant immune response and promote the release of inflammatory factors in vitro and in vivo. Mechanistically, downregulated expression of the DNA repair protein HMGB1 played a critical role in these toxic reaction processes. Overexpression of HMGB1 inhibited keratinocyte apoptosis and inflammatory reactions. Therefore, restoring HMGB1 expression might be an effective remedy against lapatinib-induced cutaneous toxicity. Finally, we found that saikosaponin A could significantly rescue the reduced HMGB1 transcription, which could alleviate lapatinib-induced DNA damage, inhibit keratinocyte apoptosis and further prevent the toxicity of lapatinib in mice. Collectively, our study might bring new hope to clinicians and tumor patients and shed new light on the prevention of cutaneous adverse drug reactions induced by EGFR inhibitors.

Prophylactic Effect of Nitric Oxide Donors on Rat Models of EGFR Inhibitor‒Induced Cutaneous Toxicities

EGF receptor (EGFR) inhibitors have been established as first-line standard-of-care therapies for nonsmall cell lung cancer but are frequently accompanied by adverse dermatological effects, in particular, acneiform rash. There is no effective clinical intervention, partially because of its poorly understood etiology. In this study, we show that inhibition of EGFR initiated keratinocyte HaCaT cell cycle arrest and apoptosis, which fueled a robust secondary inflammatory response. Rats gavaged with EGFR inhibitor showed a phenotype similar to that of clinical patients, which was in line with the interrupted functions observed in HaCaT keratinocytes. We found that a nitric oxide donor, nitroglycerin, was a feasible treatment alternative for EGFR inhibitor‒induced rash. Restoration of epidermal extracellular signal‒regulated kinase and a reduction in signal transducer and activator of transcription 3 signaling through nitroglycerin treatment rescued the cellular functions that had been damaged invitro and further ameliorated the rash in rat models. In addition, the efficacy of nitroglycerin was superior to that of existing clinical interventions. These data highlighted the importance of epidermal EGFR signaling and led to the identification of a small-molecule nitric oxide donor as a mediator that can maintain EGFR pathway functions during anti-EGFR therapies, providing a therapeutic anchor point for adverse EGFRI-induced skin effects.

Cutaneous Toxicities Associated with Immune Checkpoint Inhibitors: An Observational, Pharmacovigilance Study

Cutaneous immune-related adverse events (cirAEs) are the most prevalent complication to arise from immunotherapy and cause significant morbidity. We aimed to determine the spectrum, timing, clinical features, and outcomes of cirAEs by conducting an observational pharmacovigilance study using VigiBase, the World Health Organization's global database of individual case safety reports from over 130 member countries (ClinicalTrials.gov, number NCT04898751). We compared adverse event reporting in patients who received immune checkpoint inhibitors (91,323 adverse events) with those of the full reporting database (18,919,358 adverse events). There were 10,933 cases of cirAEs within 51 distinct dermatologic types, with 27 specific eruptions with disproportionate signal represented (information component [IC]025 > 0). Of these 27 eruptions, there were eight cirAEs with n > 100 reports, including vitiligo (IC025= 4.87), bullous pemphigoid (IC025= 4.08), lichenoid dermatitis (IC025= 3.69), erythema multiforme (IC025= 1.03), toxic epidermal necrolysis (IC025= 0.95), Stevens‒Johnson syndrome (IC025=0.41), drug eruption (IC025= 0.11), and eczematous dermatitis (IC025= 0.11). There were differences in time to onset after immune checkpoint inhibitor initiation, with a median of approximately 1 month (erythema multiforme, Stevens‒Johnson syndrome, and toxic epidermal necrolysis), 2 months (drug eruption and eczematous dermatitis), 4 months (lichenoid dermatitis), and 5‒6 months (bullous pemphigoid and vitiligo). CirAEs are diverse, dependent on cancer type, and have distinct and different onset times that are linked to the cirAE subtype.

Gut Microbiota Imbalance in Metastatic Colorectal Patients Treated With EGFRI and Long-Term Antibiotic Therapy for Cutaneous Toxicity: A Pilot Study

Patients with metastatic colorectal cancer (mCRC) frequently experience epidermal growth factor inhibitors (EGFRI)-induced skin side effects. Antibiotic treatment with doxycycline is often required in order to manage the skin and mucosal toxicity. Since these patients already have significant gut dysbiosis, the long-term antibiotic treatment may destabilize their gut microbiome.ObjectivesThe assessment of intestinal dysbiosis in patients undergoing treatment with EGFRI, who require antibiotic treatment with doxycycline in order to manage adverse skin effects.MethodsWe conducted a prospective pilot study between 2020 and 2021 involving 10 patients with mCRC. These patients were undergoing treatment with EGFRI and required either short-term or long-term treatment with doxycycline in order to manage skin toxicity.ResultsThe patients with mCRC who were treated with doxycycline for 8 weeks showed overexpression of Escherichia coli, Candida, and Geotrichum species compared to the patients who only received doxycycline treatment for two weeks.ConclusionsThe elevated levels of Escherichia coli and Candida species in the patients who received doxycycline for eight weeks compared to the patients who received the treatment for two weeks could provide a starting point for the development of a standardized guideline regarding the use of pre-active or reactive antibiotic treatment. We also highlight the importance of analyzing the intestinal microbiome of these patients. The identification of overexpressed species, as well as the deficiency of certain protective species, could guide the administration of probiotics to cover and repair the affected intestinal flora.

Skin Manifestation Induced by Immune Checkpoint Inhibitors.

In accordance with recent therapeutic progress of immune checkpoint inhibitors for certain cancers, various disorders are induced as immune-related adverse events (irAEs) affecting the skin, gut, thyroid gland, lung, and liver. Among such irAEs, mucocutaneous manifestation is the most common. Cutaneous manifestations are categorized into several groups, ie, inflammatory reactions, immunobullous reactions, alterations of epidermal keratinocytes, and alterations of epidermal melanocytes; however, there are additionally various cutaneous toxicities, unclassified into those groups. Blocking of programmed cell death 1 (PD-1)/programmed cell death ligand 1(PDL1) can lead to the induction of autoimmune reaction, via activation of cytotoxic T cells, inhibition of regulatory T cell function, and alteration of cytokine balance. Similarly, blockade of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) reduces the suppressive function of regulatory T cells. Due to those mechanisms, various autoimmune conditions can be induced, in addition to nonspecific drug eruptions. Dermatologists should be aware of various types of those mucocutaneous manifestations, either common or rare, as well as the management of such conditions. Herein, various mucocutaneous manifestations of irAEs and cases involving Japanese patients have been described, based on a single institute’s experience.

Successful Outpatient Management of Diffuse Photosensitive Bullous Dermatitis Following Pembrolizumab Therapy.

Immune checkpoint inhibitors including programmed death protein 1 inhibitors show great therapeutic benefit for numerous advanced malignancies but can cause a spectrum of immune-related adverse events, with cutaneous toxicity being a common presentation. This report includes two cases of lung adenocarcinoma treated with pembrolizumab that developed rare presentations of diffuse bullous lichenoid dermatitis involving >50% total body surface area. These cases were successfully treated in the outpatient setting with oral dexamethasone and minimal interruption of pembrolizumab therapy, a more conservative approach than current guidelines suggest. J Drugs Dermatol. 2022;21(6):668-670. doi:10.36849/JDD.6715.

The role of CYP2B6 516G>T polymorphism on efavirenz/nevirapine toxicity. Implications on treatment outcomes: Lessons from Botswana.

The two non-nucleoside reverse transcriptase inhibitors (NNRTIs), efavirenz (EFV) and nevirapine (NVP), are currently the core antiretroviral drugs for treatment of HIV in sub-Saharan Africa including Botswana. The drugs are metabolized by Cytochrome P450 2B6 (CYP2B6) liver enzyme. The CYP2B6 gene that encodes for metabolism of these drugs is known to be highly polymorphic. One of the polymorphism in the CYP2B6 gene, 516G>T, particularly the 516T allele, is known to confer poor metabolism of EFV and NVP. This may lead to high levels of plasma drug concentrations and development of treatment toxicities, like central nervous system toxicities, and cutaneous and hepatic toxicities, for EFV and NVP, respectively. The CYP2B6 516G allele on the other hand is associated with an extensive metabolism of the two NNRTIs drugs. We sought to establish association between possible developments of NNRTIs toxicities with CYP2B6 516G>T variation in Botswana.A total of 316 peripheral blood mononuclear cells samples were used in a retrospective view. All the samples were from participants on EFV/NVP-containing regimen with known toxicity output. TaqMan Real-Time PCR approach was applied for assessing CYP2B6 516 allele variation in cases with treatment toxicity and those without. Analysis was performed by chi-square statistics and logistic regression analysis.The rate of poor metabolizers among participants with toxicity and those without toxicity was 18.4% and 15.1%, respectively. The CYP2B6 516 genotype distribution comparisons between the participants with toxicity and those without were not statistically different (chi-square = .326; P = .568).CYP2B6 516 variation was not associated with NNRTI toxicity. No other factors were associated with toxicity when considering age, baseline body mass index, baseline CD4, baseline HIV viral load and adherence. The results were discussed in the context of all the studies done in Botswana to date.

"It's Like You Stuck a Pin in It:" African American/Black Patients Describe Cutaneous Toxicity From Epidermal Growth Factor Receptor Inhibitors.

Background: Epidermal growth factor receptor (EGFR) inhibitors cause cutaneous toxicity in over 90% of patients. Conceivably, healthcare providers could overlook such toxicity in African American/Black patients because of a darker complexion. This qualitative study sought to learn about such cutaneous signs and symptoms and, if present, to report them in patients' own words. Methods: Any patient who self-identified as African American/Black and who had been prescribed an EGFR inhibitor was eligible. The current report focuses on patients' responses to the following question, "What have you noticed since starting your cancer treatment (the EGFR inhibitor), any particular symptoms or reactions, positive or negative?" All interview data were audio-recorded, transcribed, and then independently coded and analyzed by two investigators. Results: Fifteen patients are the focus of this report, and all described cutaneous toxicity. Patients appeared troubled by the cosmetic aspect of these drug-induced skin changes, including their acneiform appearance, describing "little pimples with little, little pus in it." Notable were comments on hyperpigmentation, "I'm a black person but…. became darker." Furthermore, patients experienced physical symptoms: "it itches;" "it's like you stuck a pin in it;" "stinging;" and "burning;". Conclusion: Although cutaneous toxicity from EGFR inhibitors might be more difficult to visualize among darkly complected patients, the graphic descriptions offered in this qualitative study underscore the need for clinicians to heighten their awareness of such toxicity in African American/Black patients.

Nivolumab Immunotherapy-Related Skin Reactions Detected on 18F-FDG PET/CT in Renal Cell Cancer.

Nivolumab, a fully human immunoglobulin G4 anti-programmed cell death 1 antibody, provides a novel therapy option for patients with metastatic cancers. Immunotherapy agents have been associated with immune-related adverse events (irAEs), which may be detected on 18F-FDG PET/CT. Cutaneous toxicities are one of the most common irAEs in the form of maculopapular rash (eczema-like spongiotic dermatitis) and pruritus. These irAEs may lead to false-positive findings on PET/CT done during the treatment. One should be aware of the potential irAEs while interpreting PET/CT to avoid misinterpretation.

Vitiligo adverse events and associated medications as reported in the US Food and Drug Administration’s Adverse Event Reporting System from 2016 to 2021

Vitiligo adverse events and associated medications as reported in the US Food and Drug Administration’s Adverse Event Reporting System from 2016 to 2021

Efficacy and safety of tumor-treating fields in recurrent glioblastoma: a systematic review and meta-analysis.

Tumor-treating fields (TTF) is a novel cancer treatment that uses alternating electric fields to interfere with tumor cell mitosis. It has been approved by the U.S. food and drug administration for the treatment of recurrent glioblastoma (rGBM). We designed this meta-analysis to evaluate the efficacy and safety of TTF in the treatment of rGBM. The study was based on the PRISMA guideline. Systematic retrieval was performed in PubMed, Cochrane Library, and Embase databases. The outcomes were overall survival (OS) hazard ratio (HR), 1-year survival rate, and cutaneous toxicity. These studies included a total of 1048 rGBM patients who received TTF treatment. The overall survival time between the TTF group and the control group was HR 0.75 ([95%CI 0.63 to 0.89]; P = 0.001). Pooled 1-year overall survival rate and incidence of cutaneous toxicity were 0.47 and 0.48, respectively. Data were insufficient to evaluate the effect of MGMT methylation status and tumor recurrence times on heterogeneity. TTF therapy is effective for recurrent glioblastoma. However, most relevant trials should assess rGBM patient baseline characteristics such as age, KPS, MGMT methylation status, and number of tumor recurrence,. In addition, the risk of rashes caused by long-term wearing of devices should also be considered.

Toxicity profile of treatment with PD-1 inhibitors for lung cancer, melanoma and renal cell carcinoma: A real-world Brazilian study

IntroductionImmunotherapy revolutionized cancer care in the last decade and, notably among its tools, the programmed cell death protein-1 (PD-1) inhibitors. These drugs are related to increased life expectancy rates. However, they can cause several adverse events that have not been fully characterized, thus challenging clinical practice. ObjectiveTo evaluate the toxicity profile, determining its frequency, causality, and severity associated with treatment with PD-1 inhibitors in patients treated at an oncology service in the private health sector in Belo Horizonte. MethodsObservational, retrospective, and cross-sectional study, based on the review of electronic medical records. The eligibility criteria included patients over 18 years old with a diagnosis of any cancer and staging, receiving a PD-1 inhibitor from January 2017 to January 2020. ResultsThe sample consisted of 134 patients with lung cancer (46,3%), melanoma (34,3%), and kidney cancer (19,4%). The most common adverse event (AE) related to treatment were fatigue (51.5%), anorexia (23.1%), hypothyroidism (15.7%), and skin rash (14.9%), being grades 1 and 2 more prevalent. Between 3 and 12 months, there were more cutaneous, nutritional, and metabolic toxicities, and fatigue was present throughout the entire treatment period. Gastrointestinal and pulmonary toxicities were more frequent up to the 9th month. ConclusionBased on real-world evidence, it was possible to reveal important findings to support the safe practice of PD-1 inhibitors treatment. Fatigue was the most prevalent AE among patients. In addition, the kinetics of AE allowed the identification of major occurrences according to the period o treatment, allowing more precise monitoring and surveillance.

Omaveloxolone attenuates squamous cell carcinoma growth and disease severity in an Epidermolysis Bullosa mouse model.

Patients with epidermolysis bullosa (EB) are susceptible to development of squamous cell carcinomas (SCC) at sites of chronic inflammation and fibrosis. While triterpenoids such as RTA 408 (Omaveloxolone) have been shown to reduce inflammation and inhibit tumour growth in various cancer models, the utility of this class of drugs in the treatment of SCC has not been investigated. Given the dual anti-inflammatory and anti-neoplastic properties of triterpenoids, we hypothesized RTA 408 would be an effective treatment for SCCs that arise in the chronic inflammatory setting in EB. We tested the effects of topical RTA 408 on a mouse model of non-Herlitz, junctional EB. RTA 408significantly reduced phenotypic severity in the affected ears of Lamc2jeb mice. In cultures, RTA 408 reduced cell viability in EB-associated SCC cell lines and normal human epidermal keratinocytes. When administered in vivo, RTA 408 inhibited SCC tumour growth in mice without cutaneous or systemic toxicity. These results suggest that RTA 408 can be a promising new therapy to reduce inflammation and inhibit SCC growth in patients with EB.

Remodeling of dermal adipose tissue alleviates cutaneous toxicity induced by anti-EGFR therapy.

Anti-epidermal growth factor receptor (EGFR) therapy-associated cutaneous toxicity is a syndrome characterized by papulopustular rash, local inflammation, folliculitis, and microbial infection, resulting in a decrease in quality of life and dose interruption. However, no effective clinical intervention is available for this adverse effect. Here, we report the atrophy of dermal white adipose tissue (dWAT), a highly plastic adipose tissue with various skin-specific functions, correlates with rash occurrence and exacerbation in a murine model of EGFR inhibitor-induced rash. The reduction in dWAT is due to the inhibition of adipogenic differentiation by defects in peroxisome proliferator-activated receptor γ (PPARγ) signaling, and increased lipolysis by the induced expression of the lipolytic cytokine IL6. The activation of PPARγ by rosiglitazone maintains adipogenic differentiation and represses the transcription of IL6, eventually improving skin functions and ameliorating the severity of rash without altering the antitumor effects. Thus, activation of PPARγ represents a promising approach to ameliorate cutaneous toxicity in patients with cancer who receive anti-EGFR therapy.

Lichen planus pemphigoides: A unique form of bullous and lichenoid eruptions secondary to nivolumab.

The widespread use of PD‐1 inhibitors to treat various solid tumors has brought certain challenges for the clinician, including immune‐related adverse events (irAEs). Cutaneous toxicities are among the most observed irAEs. Bullous and lichenoid dermatoses following PD‐1 inhibitor therapy have been described. Here we report a novel case of lichen planus pemphigoides, featuring characteristics of both bullous pemphigoid and lichen planus, in a patient treated with nivolumab for renal cell carcinoma. We subsequently review all three cutaneous conditions which may arise in the context of PD‐1 inhibitor therapy.

Reducing Acneiform Rash Induced by EGFR Inhibitors With Honeysuckle Therapy: A Prospective, Randomized, Controlled Study.

Background: Epidermal growth factor receptor inhibitors (EGFRIs), including cetuximab, erlotinib, gefitinib and icotinib, have been proven to be effective in treating colorectal cancer or lung cancer. However, most of patients who receive EGFRIs treatment experience cutaneous toxicities, such as acneiform or papulopustular rashes, which affects quality of life and leads to discontinuation of cancer therapies. Honeysuckle is a traditional herb historically used to treat skin rash for thousands of years in Eastern Asia and showed proven safety in human. Methods: To investigate whether honeysuckle therapy could control EGFRIs induced acneiform rashes, a total of 139 colorectal and lung cancer patients with EGFRIs treatments were recruited in a prospective study. Patients were randomized to 3 arms (Arm A: prophylactic treatment with honeysuckle before rash occurred; Arm B: symptomatic treatment with honeysuckle when rash occurred; Arm C: conventional treatment with minocycline and a topical solution when rash occurred). The incidences, severities and recovery time of acneiform rash were observed in each arm. Results: Honeysuckle treatment reduced incidences of EGFRIs induced acneiform rash, which were 56.5, 68.1 and 71.7% in Arm A, B and C, respectively (p = 0.280). Severities of rash (CTCAE grade 2 and 3) were significantly lower in prophylactic honeysuckle treatment (Arm A) compared to conventional treatment (Arm C) (p = 0.027), which was 10–21%, respectively. Patients with honeysuckle treatment recovered more quickly from pruritus, the median time was 22, 36 and 58 days in Arm A, B and C, respectively (p = 0.016). Conclusion: Honeysuckle was effective in reducing incidences and severities of EGFRIs induced acneiform rash, especially for prophylactic treatment.

An overview of the efficacy of phototherapy in oncodermatology

Cutaneous adverse events (AEs) following cancer immunotherapy, targeted therapy, and chemotherapy have been well-documented in the literature. A number of case reports have identified phototherapy, a form of light therapy that mimics sunlight exposure, as a noninvasive treatment modality for these cutaneous toxicities. By inducing local suppression of the immune system, phototherapy is a skin-directed treatment with minimal effect on tumor response. Phototherapy may therefore be a viable treatment option for cutaneous AEs from cancer therapies. We reviewed the literature for patients treated with phototherapy for cutaneous AEs following cancer immunotherapy, targeted therapy, or chemotherapy. We also included three previously unpublished cases from our own institution. We identified 24 patients (80% male, mean age 67years, range 49-75years). Patients received the following phototherapy types: NB-UVB (n = 17), PUVA (n = 6), or PDT (n = 1). A topical steroid was used in conjunction with phototherapy in seven patients. At phototherapy onset, cancer treatment was either continued, temporarily discontinued, or discontinued (n = 9, 6, 7, respectively; in two cases, the cancer treatment course was unknown). Improvement of cutaneous AEs was observed in 96% of patients. Phototherapy resulted in full or partial improvement in all but one patient. A topical steroid was used in nearly a third of patients, suggesting some oncodermatologists co-administer topicals to further boost response. Continuation of cancer therapy in the majority of patients highlights an additional advantage of phototherapy. We believe phototherapy may be an effective adjunctive treatment to topical steroids when treating these cutaneous toxicities.

Cutaneous Toxicity Associated With Enfortumab Vedotin: A Real-Word Study Leveraging U.S. Food and Drug Administration Adverse Event Reporting System.

IntroductionEnfortumab vedotin (EV) has been demonstrated to have a significant response rate in early phase trials and is known for its tolerable side-effect profile. Emerging case reports have raised awareness of cutaneous toxicities, which may be a potentially fatal complication.ObjectiveTo assess the potential relevance between EV and cutaneous toxicities reports through data mining of the U.S. Food and Drug Administration (FDA) adverse event reporting system (FAERS).MethodsData from January 1, 2019, to November 4, 2021, in the FAERS database were retrieved. Information component (IC) and reporting odds ratio (ROR) were used to evaluate the association between EV and cutaneous toxicities events.ResultsEV was significantly associated with cutaneous toxicities in the database compared with both all other drugs (ROR 12.90 [10.62–15.66], IC 2.76 [2.52–3.01], middle signal) and platinum-based therapy (ROR 15.11 [12.43–18.37], IC 2.91 [2.66–3.15], middle signal) in the FAERS database. A significant association was detected between EV and all the cutaneous adverse effects (AEs) except erythema, palmar–plantar erythrodysesthesia syndrome, and dermatitis allergic. Both Stevens–Johnson syndrome and toxic epidermal necrolysis occurred 15 times as frequently for EV compared with all other drugs (ROR = 15.20; ROR = 15.52), while Stevens–Johnson syndrome occurred 18 times and toxic epidermal necrolysis occurred 7 times as frequently for EV compared with platinum-based therapy in the database (ROR = 18.74; ROR = 7.80). All groups that limited the gender and age showed a significant association between EV and cutaneous toxicities.ConclusionsA significant signal was detected between EV use and cutaneous toxicities. It is worth noting that Stevens–Johnson syndrome and toxic epidermal necrolysis were significantly associated with EV use.