Cutaneous Skin Toxicities of Oncological Targeted Therapies: Comprehensive Overview of Mechanisms, Management, and Research Gaps-A Narrative Review.

Key Summary Points

An increasing number of patients are in need of treatment due to targeted therapy-related dermatological adverse events. This interdisciplinary topic is not frequently discussed among dermatologists, and summarized data on agents other than immune checkpoint inhibitors is hard to find. This review summarizes all clinically relevant target therapies, their mechanisms of action, and management of their most common cutaneous adverse events. Correct and early identification of cutaneous adverse events allows optimized management of oncological treatment, reducing the need for dose modifications and treatment discontinuations.

Introduction

The introduction of targeted therapies in oncology has transformed cancer treatment. A significant portion of oncological patients are receiving therapeutic agents targeting specific molecules and pathways. For example, epidermal growth factor receptor (EGFR) mutations play a crucial role in multiple malignancies, leading to a growing number of therapies specifically targeting this pathway in recent years [ 1 ]. However, side effects frequently occur, posing a major obstacle both to oncologists and other clinicians including dermatologists [ 2 ]. Depending on the drug and its mechanism of action, cutaneous side effects of targeted treatments can occur in up to 90% of patients receiving them [ 3 ]. These cutaneous toxicities can result in preventable dose reduction or treatment cessation, especially when treated inadequately. There is high-quality evidence that supports the introduction of skin-targeted dermatological management of cutaneous adverse events (CAEs) in order to reduce their severity and impact on patients’ quality of life (QoL) [ 4 ]. With multiple new molecules and entire drug classes currently in development, this field of dermatology is dynamically expanding. However, most research and numerous guidelines are focused on immune checkpoint inhibitors (ICI; drugs targeting checkpoint inhibitors such as PD-1, PD-L1, or CTLA4), leaving other drug classes underrepresented. The scope of this review is to summarize the relevant CAEs of currently utilized targeted therapies (excluding ICI) as well as to outline their management, supportive care, and identify gaps in research.

Methodology

The objective of this narrative review was to identify, summarize, and critically evaluate clinical evidence regarding current epidemiology and management of non-ICI targeted therapy-related dermatological AEs. The literature search was performed in PubMed/MEDLINE and Google Scholar, using the following terms and their combinations: “cutaneous toxicities,” “dermatological adverse events,” “targeted therapies,” “oncology,” “dermatology,” “skin adverse events,” “management,” “EGFR inhibitors,” “BRAF inhibitors,” “MEK inhibitors,” “HER2 inhibitors,” “CDK4/6 inhibitors,” “VEGFR inhibitors,” “Hedgehog inhibitors,” “FGFR inhibitors,” “antibody–drug conjugates,” “CCR-4″,“talquetamab,” “tebentafusp,” “rash,” “acneiform rash,” “pruritus,” “alopecia,” “hand–foot syndrome,” “palmar-plantar dysesthesia,” “lichenoid reactions,” “lichen planus,” “supportive care,” “exosomes“,“bioferments,” “skincare.” Synonyms and related terms were included in the search. Titles and abstracts were screened for relevance. Only peer-reviewed articles published in English published between January 1, 2000 and October 30, 2025 were considered. The search was extended to relevant papers cited in reference lists of included articles. Data was synthesized narratively and, where possible, summarized in tables. This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

Targeted Therapy Drug Classes

EGFR Inhibitors (EGFR-i) and Anti-EGFR Antibodies

Common side effects of treatments that target the EGFR include rash, erythema, and acneiform dermatitis [ 5 ]. Xerosis and pruritus are present in the majority of patients, most commonly in those treated with panitumumab [ 6 , 7 ]. Acneiform dermatitis, an acne-like monomorphic pustulopapular eruption, is observed in up to 90% of patients receiving anti-EGFR treatment, more commonly with monoclonal antibodies (i.e., panitumumab, cetuximab) than with tyrosine kinase inhibitors (i.e., erlotinib, gefitinib). The lesions can be pruritic and cover large areas of the face, neck, and body in patterns that are not typical for acne. The incidence of acneiform eruption is associated with a favorable response to treatment [ 8 ]. An exact mechanism of EGFR-i-associated acneiform eruptions has yet to be completely elucidated, but upregulation of the p27 protein, which causes abnormal keratinocyte proliferation, is currently considered to be one of the main causal factors [ 9 ]. Nail and hair toxicities such as paronychia and trichomegaly have also been frequently reported [ 10 , 11 ]. Skin toxicities are the most common cause of treatment dose reduction during EGFR therapy with first-generation (gefitinib, erlotinib) and second-generation (afatinib, dacomitinib) tyrosine kinase inhibitors (TKIs), and frequently multiple skin toxicities can occur in one patient at one time [ 12 ].

Amivantamab, a newer-generation antibody blocking both EGFR and mesenchymal epithelial transition factor, has caused erosive pustular dermatosis of the scalp (EPDS), in 21.9% of patients, with a significant percentage of the cases (28.5%) requiring dose reduction or treatment cessation [ 13 ]. Other EGFR-i are not very frequently associated with EPDS, but its incidence during EGFR-i treatment has been reported [ 14 ].

BRAF and MEK Inhibitors

BRAF inhibitors can be used as monotherapy or combined with MEK inhibitors in treating BRAF-mutated melanoma. The most common cutaneous toxicities of these drugs include rashes, alopecia, hyperkeratosis, and photosensitivity, which are more frequently observed with vemurafenib than with dabrafenib [ 15 , 16 ] (Table 1 ). It is, however, notable that combination BRAF/MEK therapy causes fewer adverse cutaneous events than BRAF monotherapy. Incidence of cutaneous squamous cell carcinoma post-BRAF therapy has been reported [ 17 ]. MEK inhibitors can also induce acneiform rashes [ 18 ]. Table 1 Comparison of cutaneous toxicities of BRAF/MEK and BRAF therapies [ 15 – 17 ] Toxicity type BRAF/MEK combination therapy (%) BRAF alone (%) Rash 14–41 22–43 Alopecia 10–20 37–39 Hyperkeratosis 4–10 25–39 Photosensitivity 4–10 22–39 cuSCC/keratoacanthoma 1–4 12–36 Skin papilloma 1–2 23 Pruritus/dry skin 10–20 10–20 cuSCC cutaneous squamous cell carcinoma

HER2/HER

The frequency of cutaneous toxicities depends on the molecular mechanism of human epidermal growth factor receptor 2 (HER2)/HER inhibition due to different ways of interaction with the pathway (Table 2 ). Whereas monoclonal antibodies induce cutaneous adverse reactions in approximately 1% of patients, TKIs cause these events more frequently as a result of direct inhibition of the EGFR pathway in keratinocytes [ 19 – 21 ]. Palmar-plantar erythrodysesthesia (PPE), also known as hand‒foot syndrome (HFS), is reported during treatment with multiple TKIs, including those targeting HER2/HER [ 22 ]. It manifests as paresthesia with tingling, numbness or burning sensations, as well as painful erythema of the hands and feet, which, in severe cases, may progress to skin ulceration [ 23 ]. Table 2 Comparison of cutaneous skin toxicities during anti-HER2/HER therapy with monoclonal antibodies and tyrosine kinase inhibitors [ 19 , 24 ] Drug Common cutaneous toxicities Frequency (all grades) Severe (≥ Grade 3) Trastuzumab, pertuzumab Rash ~ 1% Rare Lapatinib Rash, PPE Rash 27–52%, PPE 49% Rash 1–4%, PPE 7% Neratinib Rash 10%, PPE 46% Rash 0%, PPE 10% Pyrotinib Rash 5%, PPE 79% Rash 2%, PPE 26% Tucatinib Rash 20%, PPE 63% Rash –, PPE 13% PPE palmar-plantar exanthema/erythrodysesthesia

CDK4/6 Inhibitors

Inhibitors of CDK (cyclin-dependent kinase) 4 and 6 are used in treating metastatic breast carcinoma. They are associated with numerous AEs, and cutaneous toxicities account for 15% of them [ 25 ] (Table 3 ). However, despite their common occurrence they are mostly mild and rarely cause treatment cessation or dose adjustment [ 26 ]. CDK4/6 inhibitors might commonly cause pruritus (62%) alopecia (32%), eczema (31%), and vitiligo-like lesions (27%), with significant differences between the three drugs of this class, probably due to their varying selectivity towards CDK4 and CDK6 [ 27 ]. Although abemaciclib demonstrates a more favorable cutaneous safety profile due to its CDK4 selectivity, alopecia is commonly reported in treated patient [ 28 ]. Table 3 Comparison of cutaneous adverse events (AEs) between CDK4/6 inhibitors [ 27 , 29 – 31 ] Drug Skin-related AEs Hair-related AEs Palbociclib Pruritus 46% Eczema 33% Rash 25% Vitiligo-like lesions 4–12% Lichenoid reactions 8% Alopecia 37% Abemaciclib Pruritus 13% Rash 11–17% Alopecia 15–33% Ribociclib Pruritus 68% Eczema 29% Rash 20% Vitiligo-like lesions 37–88% Lichenoid reactions 7% Alopecia 27%

Multikinase and VEGFR Inhibitors

Most multikinase inhibitors, including those targeting the vascular epithelial growth factor receptor (VEGFR) pathway, inhibit other kinase pathways with varying specificity and effectiveness. AEs including pruritus, rashes, and HFS are regularly seen in patients receiving anti-VEGFR drugs [ 32 ]. HFS in patients treated with sorafenib for metastatic renal cell carcinoma is an independent favorable prognostic factor for treatment outcomes such as tumor response and progression-free survival [ 22 ]. The incidence of HFS varies between different agents, e.g., with sorafenib causing HFS in 37% of patients, pazopanib in only 9%, and no significant incidence observed in groups treated with vandetanib [ 33 ]. The lack of significant incidence of HFS in patients receiving vandetanib is explained by the fact that concurrent inhibition of VEGFR and platelet-derived growth factor receptor (PDGFR) is postulated to be a prerequisite to cause HFS [ 34 ]. Vandetanib inhibits VEGFR, but does not impact the PDGFR pathway. Imatinib mesylate, a multikinase inhibitor that mainly inhibits the Bcr-Abl kinase, also inhibits PDGFR, but not VEGFR. It does not cause HFS [ 35 ]. Imatinib mesylate causes dermatological AEs in 31–44% of patients, most commonly a maculopapular rash on the trunk and forearms, but pigmentation disorders, lichenoid or morbilliform reactions may appear as well [ 36 ].

Hedgehog Pathway Inhibitors

Sonic hedgehog (Shh) pathway inhibitors—vismodegib and sonidegib—are a mainstay in therapy of locally advanced and metastatic basal cell carcinoma. Since the Shh pathway is linked to homeostasis of the hair follicle, absence of signalling causes decrease in hair growth and prevents hair follicles from entering the anagen phase [ 37 ]. Diffuse, gradual alopecia is the most common CAE of Hedgehog inhibitors and it has a large impact on patients’ QoL. Despite this fact, there are no established treatments and no studies have been published on the effectiveness of any intervention to prevent or treat Shh inhibitor-associated alopecia. Sonidegib is associated with lower incidence of alopecia than vismodegib, but extracutaneous AEs are more common in sonidegib [ 38 ] (Table 4 ). Incidence of secondary squamous cell carcinoma (SCC) during Shh inhibitor treatment is reported; however, as a result of uncertainties regarding mechanism, follow-up, and low reproducibility of statistical significance between studies, this AE is still debated [ 38 ]. Table 4 Comparison of the frequency of cutaneous adverse events of Hedgehog inhibitors [ 38 – 40 ] Toxicity type Vismodegib (%) Sonidegib (%) Alopecia 31–66 14–51 Secondary squamous cell carcinoma 1–11 < 1–3

Antibody–Drug Conjugates

Antibody–drug conjugates (ADC) use monoclonal antibodies to deliver targeted drugs to tumor-associated antigens in a precise manner. However, since those antigens can be expressed in non-neoplastic tissue, on-target off-tumor effects may occur, resulting in a range of toxicities [ 41 ] (Table 5 ). For example, CD44v6, a target antigen for bivatuzumab mertansine (BM, an ADC carrying an antimicrotubule agent) investigated for SCC of the head and neck, is expressed in healthy squamous epithelium which causes desquamation in up to 80% of patients treated with BM [ 42 , 43 ]. There are also significant differences between the incidence of cutaneous toxicities in ADCs targeting the same antigen, but carrying different payloads with a different linker stability; for instance, the difference between incidence of alopecia in two HER2-targeting trastuzumab-based ADCs trastuzumab emtansine and trastuzumab deruxtecan is substantial: 0.3–6.6% and 36.2–49.8, respectively [ 44 ]. Table 5 Antibody–drug conjugates (ADCs) most commonly associated with cutaneous toxicities [ 41 – 50 ] ADC name Target antigen Key cutaneous toxicities Frequency Trastuzumab emtansine (T-DM1) HER2 Rash, alopecia Rash up to 12% Alopecia < 1–6% Trastuzumab deruxtecan (T-DXd) HER2 Alopecia 36–50% Sacituzumab govitecan (SG) Trop2 Rash, pruritus, alopecia Rash 9–28% Alopecia 38–90% Brentuximab vedotin (BV) CD30 Rash, alopecia, xerosis Rash 62% Alopecia 20% Xerosis 13% Enfortumab vedotin (EV) Nectin-4 Rash, pruritus, alopecia, severe skin reactions Rash 40–62%, Alopecia 20–49% Pruritus 42% SJS/TEN rare Bivatuzumab mertansine (BM) CD44v6 Skin desquamation, TEN Desquamation ~ 80% TEN toxic epidermal necrolysis, SJS Stevens–Johnson syndrome

FGFR1–4 Inhibitors

Inhibitors of fibroblast growth factor receptors (FGFRs) are used to treat cholangiocarcinoma and urothelial carcinoma. Since FGFRs are widely expressed in the skin, hair follicles and nail tissues, cutaneous toxicities are often observed during treatment with FGFR inhibitors, as FGF regulates keratinocyte proliferation, tissue repair, and can impact hair growth [ 51 ] (Table 6 ). Alopecia is the most commonly reported dermatological AE [ 51 ]. CAEs are more common in FGFR2-selective inhibitors than in pan-FGFR inhibitors [ 52 ]. These CAEs often respond to topical treatment and are rarely high-grade; treatment modification or discontinuation is rare [ 53 ]. Table 6 CAEs associated with FGFR inhibitors [ 51 , 53 ] Drug Skin toxicities Hair toxicities Nail toxicities Erdafitinib Dry skin 35% (0–6% ≥ G3) HFS 23–29% (0–5% ≥ G3) Alopecia 29% Onycholysis 18% (2% ≥ G3) Paronychia 17–24% (3–6% ≥ G3) Nail dystrophy 16–29% (6% ≥ G3) Pemigatinib Dry skin 0–16% (0–1% ≥ G3) HFS 0–15% (0–4% ≥ G3) Alopecia 40–49% (1% ≥ G3) Onychomadesis 0–10% Nail discoloration 8–10% (1% ≥ G3) Futibatinib Dry skin 13–27% HFS 13–18% (1–4% ≥ G3) Rash 0–10% Alopecia 19–30% Nail disorder 0–16% Derazatinib Dry skin 10% Pruritus 10% Dermatitis 7% Alopecia 24% N/R Rogaratinib Dry skin 14% Alopecia 20% N/R Infigratinib Dry skin 12–18% HFS 12–21% (5–8% ≥ G3) Rash 7% Maculopapular rash 7% (2% ≥ G3) Alopecia 26–31% Nail disorder 21% Nail discoloration 8% Paronychia 7% Onychomadesis 18% N/R not reported, HFS hand–foot syndrome/palmar-plantar dysesthesia, G3 grade 3, N/R not reported

CC Chemokine Receptor 4

Mogamulizumab is a monoclonal anti-CC chemokine receptor 4 (CCR-4) antibody used in treatment of cutaneous T cell lymphoma (CTCL). CCR-4 is expressed on malignant T cells in 30–65% of patients with peripheral T cell lymphomas, including CTCL [ 54 ]. CCR-4 is a molecule that is implicated in skin accumulation—epidermotropism—of T cells [ 55 ]. However, since CCR-4 is expressed on regulatory T cells (Treg) and Th17 cells, whose depletion impacts skin homeostasis, mogamulizumab causes an increase in proliferation of CD8 + T cells [ 56 ]. Those CD8 + cells are mostly newly formed autoreactive clones which have been linked to the high frequency of CAEs during the treatment with mogamulizumab [ 57 ].

Up to 50–63% of patients receiving mogamulizumab may develop cutaneous toxicities—including maculopapular and papulosquamous rashes, psoriasis, toxic eruptions, and vitiligo [ 58 – 60 ]. However, these rashes may resemble CTCL progression and histopatological examination with T cell clonality testing may be helpful to differentiate them [ 61 ]. Development of dermatological AEs may predict a favorable treatment response [ 62 ]. The onset of these AEs is reported usually after the fourth or subsequent infusions [ 59 ].

Anti-(HLA)-A*02:01

Tebentafusp, approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) for treatment of metastatic uveal melanoma, is an immune cell-mobilizing monoclonal T cell receptor against cancer, combining an HLA-A*02:01-restricted T cell receptor specific for the glycoprotein 100 (gp100) peptide, binding to gp100-positive cells. Cutaneous toxicities appear in approximately 80% of patients, with rash being the most common presentation and a predictor of longer median overall survival rate, especially when developed after three doses of the drug at least once [ 63 , 64 ]. Tebentafusp-related rash presents as symmetrical erythematous patches on the face, neck, and trunk, frequently involving periorbital areas with accompanying periorbital edema [ 63 ]. Vitiligo-like lesions can also be observed [ 65 ].

Anti-CD3 and GPRC5D

Bispecific antibodies target two antigens simultaneously. Talquetamab is a bispecific antibody targeting CD3 and G protein-coupled receptor, family C, group 5, member D (GPRC5D) in a 1:1 configuration to treat multiple myeloma by recruiting and activating T cells. Since GPRC5D can be expressed in the skin and hair follicles, on-target and off-tumor cutaneous toxicities of talquetamab are frequent. Skin-related AEs observed in a phase one study were noticed in 67% of patients receiving the drug weekly and 70% of patients receiving the drug every second week [ 66 ]. In the phase 2 MonumenTAL-1 study 56–71% of patients developed CAEs and 61% reported nail AEs [ 67 ]. Rashes were reported in 35% of patients receiving talquetamab [ 68 ].

Between bispecific antibodies that target the same antigens the difference in affinity towards those antigens can result in a vastly varying AE profile. Forimtamig, an antibody targeting CD3 and GPRC5D in a 2:1 configuration, has been investigated in a phase 1 clinical study with 78–86% of patients exhibiting skin AEs, 24–28% nail AEs and 73–77% mucosal toxicity-associated AEs [ 68 ].

Management of Cutaneous Toxicities

Dermatological AEs of oncological therapies can be classified using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 published in 2017, outlining the grading of different CAEs in order to provide a better structure for standardized management, both dermatological and oncological [ 69 ]. Selected CAEs relevant to targeted therapies and their grading are listed in Table 7 . Table 7 Grading of selected dermatological AEs adapted from the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 [ 69 ] Cutaneous toxicity Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 Alopecia Hair loss of < 50% of normal for that individual that is not obvious from a distance but only on close inspection, a different hair style might be required to cover the hair loss, but it does not require a wig or hairpiece to camouflage Hair loss of ≥ 50% normal for that individual that is readily apparent to others; a wig or hair piece is necessary if the patient desires to completely camouflage the hair loss; associated with psychosocial impact – – – Bullous dermatitis Asymptomatic, blisters covering < 10% BSA Blisters covering 10–30% BSA; painful blisters; limiting instrumental ADL Blisters covering > 30% BSA; limiting instrumental ADL Blisters covering > 30% BSA; associated with fluid or electrolyte abnormalities; ICU care or burn unit indicated Death Dry skin Covering < 10% BSA and no associated erythema or pruritus Covering 10–30% BSA and associated with erythema or pruritus; limiting instrumental ADL Covering > 30% BSA and associated with pruritus; limiting self-care ADL – – Eczema Asymptomatic or mild symptoms; additional medical intervention over baseline not indicated Moderate; topical or oral intervention indicated; additional medical intervention over baseline indicated Severe or medically significant but not immediately life-threatening; IV intervention indicated – – Erythema multiforme Target lesions covering < 10% BSA and not associated with skin tenderness Target lesions covering 10–30% BSA and associated with skin tenderness Target lesions covering > 30% BSA with oral or genital erosions Target lesions covering > 30% BSA; associated with fluid or electrolyte abnormalities; ICU or burn unit indicated Death Erythroderma – Erythema covering > 90% BSA without associated symptoms; limiting instrumental ADL Erythema covering > 90% BSA with symptoms (pruritus, tenderness); limiting self-care ADL Erythema covering > 90% BSA, with fluid or electrolyte abnormalities; ICU or burn care indicated Death Palmar–plantar erythrodysesthesia Minimal skin changes or dermatitis (erythema, edema, hyperkeratosis) without pain Skin changes (peeling, blisters, bleeding, fissures, edema, hyperkeratosis) with pain; limits instrumental ADL Severe skin changes with pain; limiting self-care ADL – – Photosensitivity Painless erythema and erythema covering < 10% BSA Tender erythema covering 10–30% BSA Erythema covering > 30% BSA with blistering; photosensitivity; oral corticosteroids and pain control indicated Life-threatening consequences; urgent intervention indicated Death Pruritus Mild or localized; topical intervention indicated Widespread and intermittent; secondary skin changes from scratching; oral intervention indicated; limits instrumental ADL Widespread and constant; limiting self-care ADL or sleep; systemic corticosteroids or immunosuppressive therapy indicated – – Rash acneiform Papules/pustules covering < 10% BSA; may or may not have pruritus or tenderness Papules/pustules 10–30% BSA; possible pruritus/tenderness; psychosocial impact; limits instrumental ADL Papules/pustules covering > 30% BSA with or without mild symptoms Papules/pustules > 30% BSA with moderate/severe symptoms; limits self-care ADL; local superinfection requiring oral antibiotics Life-threatening; extensive superinfection requiring IV antibiotics Death Rash maculopapular Macules/papules < 10% BSA with/without symptoms (e.g., pruritus) Macules/papules 10–30% BSA with/without symptoms; limits instrumental ADL Rash covering > 30% BSA with or without mild symptoms Macules/papules > 30% BSA with moderate/severe symptoms; limits self-care ADL – – Skin hypopigmentation < 10% BSA; no psychosocial impact > 10% BSA; psychosocial impact Stevens–Johnson syndrome – – Skin sloughing < 10% BSA with signs (erythema, purpura, epidermal and mucous membrane detachment) Skin sloughing 10–30% BSA with skin symptoms (erythema, purpura, epidermal detachment) Death Toxic epidermal necrolysis – – – Skin sloughing ≥ 30% BSA with symptoms (erythema, purpura, epidermal and/or mucous membrane detachment) Death Skin and subcutaneous disorders—other Asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL Severe or medically significant but not immediately life-threatening; hospitalization indicated; limiting self-care ADL Life-threatening consequences; urgent intervention indicated Death ADL activities of daily living, BSA body surface area, IV intravenous, ICU intensive care unit

Dose modification and especially discontinuation of the treatment should be a shared decision-making process between the dermatologist and oncologist, involving a careful risk/benefit assessment [ 70 ]. Oncologists are more likely to overestimate the grade of a CAE than dermatologists, which can cause premature treatment decisions [ 71 ]. The decision to discontinue treatment should incorporate a patient’s preferences as well.

Since non-ICI targeted therapies are remarkably diverse in their mechanisms of action and profiles of AEs, the data on the treatment of CAEs related to them is relatively scarce, with the notable exception of EGFR-related acneiform rashes. In clinical practice management of non-ICI CAEs is oftentimes similar to the management of respective ICI CAEs, with treatment regimens yielding results despite the mechanistic differences between them. There is also a lack of research directly comparing the epidemiology, timing, and morphology of ICI-related and non-ICI-related CAEs of different classes. However, we hope that with an increasing number of patients treated with these drugs, more research dedicated to other targeted therapies might result in dedicated treatment guidelines in the future, closing this notable research gap and improving patient outcomes.

Pruritus

Pruritus significantly impacts patients’ QoL. While it is one of the most common CAEs related to oncological targeted treatment, only a minority of cases are high-grade and require an escalation of treatment beyond topical corticosteroids and oral antihistamines (Table 8 ) [ 7 ]. Biologic agents such as omalizumab and dupilumab are helpful in treatment-resistant cases [ 72 , 73 ]. Table 8 Management of treatment-related pruritus [ 7 , 73 – 75 ] Severity Grade 1 Grade 2 Grade 3 Skin-directed therapy Fragrance-free emollient moisturizers, applied regularly Humidifier use Restricting bath and shower time, using lukewarm water and mild soap-free skin cleansers Potent/superpotent topical CS once-twice daily Systemic therapy Oral antihistamines (non-sedating) once daily Oral antihistamines (non-sedating) once daily Consider replacing antihistamines with GABA analogues—gabapentin or pregabalin If persistent, consider neurokinine 1 receptor antagonists, e.g., aprepitant or biologic agents—dupilumab or omalizumab Consider oral CS—prednisone at a 0.5–1 mg/kg dose with a 14 day taper GABA analogues—gabapentin or pregabalin Consider omalizumab or dupilumab Impact on oncological treatment Continue treatment Continue treatment Withhold until grade 1/2 or discontinue (multidisciplinary decision) Reassessment 2–4 weeks 2–4 weeks As needed CS corticosteroids

Maculopapular Rash

Maculopapular rash can appear as an exanthematous or morbilliform eruption mainly on the trunk and extremities, with or without preceding pruritus [ 76 ]. Management of maculopapular rashes is outlined in Table 9 . Table 9 Management of maculopapular rash [ 73 – 75 ] Severity Grade 1 Grade 2 Grade 2 (persistent/intolerable) Grade 3 Grade 4 (life-threatening) Skin-directed therapy Fragrance-free emollient moisturizers, applied regularly Restricting bath and shower time, using lukewarm water and mild skin cleansers Potent/superpotent topical CS once-twice daily Urgent supportive measures Systemic therapy Oral antihistamines (non-sedating) once daily Oral antihistamines (non-sedating) once daily Consider oral CS—prednisone at a 0.5–1 mg/kg dose increasing to 2 mg/kg when no improvement Consider biologics—tocilizumab, infliximab, dupilumab Methyloprednisolone 2 mg/kg/day or equivalent Impact on oncological treatment Continue treatment Withhold until grade 0/1 and prednisone taper < 10 mg daily Permanently discontinue Reassessment 2–4 weeks 2–4 weeks, start CS taper upon improvement As needed CS corticosteroids

Acneiform Eruptions

Acneiform eruptions are the most common dermatological AEs of EGFR-i. Since they are known to have a significant negative QoL impact, their incidence and lack of adequate management can lead to premature treatment discontinuation [ 77 ]. Acneiform eruptions do not respond to classic acne treatments, such as retinoids or salicylic acid, which should be avoided. Prophylaxis using daily applications of topical emollients and sunscreen with an SPF factor of more than 30 is recommended. Most recently, the 2025 EU/USA Delphi consensus supports the aforementioned skincare regimen as prophylaxis and indicates the use of twice daily medium-potency topical steroids with systemic doxycycline (100–200 mg/day) for preemptive treatment used for 6–8 weeks after starting anti-EGFR therapy, discontinued if no acneiform rash is observed (Table 10 ) [ 78 ]. Table 10 Management of acneiform eruptions [ 78 ] Severity Grade 1 Grade 2 Grade 3 Grade 4 (life-threatening superinfection) Skin-directed therapy Topical fragrance-free emollient use daily Daily application of sunscreen with SPF30 or higher Avoidance of irritative products Topical steroids (mild on the face, medium on the body) or calcineurin inhibitors as steroid-sparing agents Topical fragrance-free emollient use daily Daily application of sunscreen with SPF30 or higher Avoidance of irritative products Topical steroids (strength and application frequency tailored to patient’s severity) or calcineurin inhibitors as steroid-sparing agents Perform swab cultures Urgent supportive measures Systemic therapy Antihistamines if pruritus present Doxycycline 100–200 mg daily Doxycycline 200 mg daily/minocycline if UV sensitivity Antihistamines if pruritus present Consider low doses of isotretinoin if not responding to doxycycline/minocycline Intravenous antibiotics in line with antibiogram results Impact on oncological treatment Continue treatment Continue treatment Continue treatment Withhold if clinically justified until grade < 3 Discontinue if clinically justified Reassessment 2–4 weeks 2–4 weeks, start corticosteroids taper upon improvement As needed

However, it is worth noting that treatment strategies focused on molecular pathways of certain CAEs have also not been investigated, such as the increase of p27 protein expression in keratinocytes during anti-EGFR therapy that is postulated to cause acneiform eruptions [ 9 ]. It is possible that reduction of p27 expression using topical preparations can be beneficial. However, mechanistic interventions are not always effective—studies with topical growth factors in treating EGFR-i-associated acneiform eruptions have yielded mixed results [ 79 ].

Vitiligo

Most cases of CDK4/6-associated vitiligo-like AEs are mild and very rarely a reason for treatment discontinuation [ 80 ]. Treatment guidelines are summarized in Table 11 . Table 11 Management of vitiligo-like lesions [ 74 , 75 ] Severity Grade 1 Grade 2 Intervention Photoprotection No treatment (shared decision with the patient) Consider potent topical corticosteroids/calcineurin inhibitors Photoprotection No treatment (shared decision with the patient) Consider potent topical corticosteroids/calcineurin inhibitors/narrowband UVB therapy Impact on oncological treatment Continue treatment Continue treatment Reassessment 2–4 weeks 2–4 weeks

Lichen Planus-Like Rash

Lichen planus (LP)-like CAEs can present both as a typical pruritic papular eruption and as other less common LP subtypes [ 81 ]. While more frequently associated with immunotherapy with anti-programmed death 1/programmed death ligand 1 (PD-1/PD-L1) drugs, they can also appear in patients receiving anti-CDK4/6 agents. Glucocorticoids, both topical and oral, are a cornerstone of treatment (Table 12 ). Table 12 Management of lichen planus-like rash [ 74 , 75 ] Severity (grade as rash) Grade 1 Grade 2 Grade 2 (intolerable or with severe mucosal involvement) Grade 3 Recalcitrant Intervention Topical potent/superpotent CS (up to twice a day) Oral antihistamines Uphold topical treatment Consider oral CS (0.5–1 mg/kg prednisone for 4–6 weeks) Consider adding oral retinoids (20–30 mg/day) according to the clinical presentation Continue oral CS at a 1 mg/kg dose Consider other treatment modalities and steroid-sparing agents: UVB phototherapy (non-melanoma), methotrexate, biologic agents (infliximab, tocilizumab, dupilumab, omalizumab) Impact on oncological treatment Continue treatment Withhold treatment if clinically justified until grade 1 (and CS taper < 10 mg/day) Withhold or discontinue if clinically justified Reassessment 2–4 weeks 2–4 weeks If LP rash does not improve escalate therapy If there is improvement—start CS taper As needed CS corticosteroids

Oral lichen planus can present as reticulated, erosive or bullous lesions and should be differentiated from autoimmune bullous diseases with histopathology and immunofluorescence to be managed properly. Appropriate topical preparations of CS including mouthwashes and solutions are helpful in grade 1–2 oral lesions, and systemic treatment (Table 12 ) is often needed in more severe grade 2–3 lesions [ 75 ]. The incidence rate of oral lichen planus-like lesions in non-ICI therapy has not been reported.

Hand–Foot Syndrome

Palmar–plantar erythrodysesthesia, known as hand‒foot syndrome (HFS), is the most commonly reported adverse reaction to classical chemotherapeutics including 5-fluorouracil (5-FU), capecitabine, and liposomal doxorubicin. HFS and hand‒foot skin reaction (HFSR) can also be induced by multikinase inhibitors (TKI). Topical 10% urea emollients are helpful for HFS prevention [ 82 ]. However, good-quality data regarding reactive treatment in TKI-related HFS is scarce. Grade 2 HFS can be managed by transient dose reduction, and grade 3 HFS treatment discontinuation is advised [ 83 ].

Alopecia

Alopecia is a frequent CAE reported during treatment with multiple targeted therapies. Prophylactic measures used in prevention of chemotherapy-induced alopecia such as scalp cooling are not recommended for use in targeted therapy-related alopecia and there is no evidence to support it. Most research is focused on FGFR inhibitor-related alopecia, in all cases of which topical minoxidil is recommended [ 51 ]. Oral minoxidil has been explored in a cohort study of patients receiving anti-CDK4/6 therapies with 80% of patients showing improvement in hair density after 4–6 months of treatment with no serious adverse effects [ 84 ]. The favorable safety profile and high efficacy of low-dose oral minoxidil in treating hair loss warrants its further exploration in alopecia caused by other targeted therapies.

Erosive Pustular Dermatosis of the Scalp (EPDS)

EDPS is an emerging CAE frequently reported during treatment with amivantamab and rarely with EGFR-i [ 13 , 85 ]. EPDS is an inflammatory disorder of the scalp in which erosions, thick crusts, and pustules exuding a serum-hematic liquid appear, leading to skin atrophy and scarring alopecia [ 86 ]. About 18% of patients require dose alteration or treatment discontinuation due to EPDS [ 14 ]. Prophylaxis with an adequate skincare regimen and systemic tetracyclines can decrease its severity [ 4 ]. Mild forms of EPDS are usually treated with high-potency topical corticosteroids, topical antibiotics, and oral tetracyclines (100–200 mg daily) [ 87 ]. More severe and recalcitrant cases may require systemic corticosteroids or systemic retinoids [ 14 ].

Stevens–Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN)

In cases of severe drug reactions such as SJS and TEN the causal targeted therapy should be discontinued. Other than urgent admission to a specialized ward with adequate supportive care, treatment with glucocorticosteroids and cyclosporine is usually recommended [ 74 ]. However, etanercept, a tumor necrosis factor alpha inhibitor, has been shown to improve survival and skin healing time in TEN [ 88 ]. One case report describing the use of etanercept combined with other treatment modalities in the treatment of TEN caused by anti-PD-1 therapy has been published [ 89 ].

Supportive Care: Future Perspectives

Future strategies for the prevention and management of treatment-related cutaneous toxicities are exploring approaches centered in skin biology, aimed towards restoring skin barrier function and cutaneous homeostasis. Among these, the use of bioferments—components obtained from natural raw materials of plant origin through fermentation with selected strains of microorganisms—emerge as a potential option for managing xerosis and barrier impairment, primarily owing to their antipruritic and moisturizing properties [ 90 – 92 ]. Although microbiome-supporting interventions have not yet been validated in controlled clinical studies, the growing recognition of the skin microbiome’s role in epidermal integrity underscores their relevance as promising avenues for further investigation.

In parallel, exosomes represent an additional emerging therapeutic perspective. These nanosized extracellular vesicles (30–150 nm) secreted by various cell types, including mesenchymal stem cells (MSC), immune cells, and keratinocytes, involved in intercellular communication, have demonstrated anti-inflammatory and regenerative effects in preclinical models [ 93 ], suggesting a potential role in counteracting inflammation-driven keratinocyte damage and barrier dysfunction induced by targeted therapies. While clinical evidence remains limited, the possibility of integrating exosome-based approaches with established dermatologic supportive care [ 94 ], as well as the development of personalized formulations [ 95 ], highlights their translational potential. Further clinical validation will be required before these strategies can be incorporated into routine practice.

Conclusions

A tailor-made regimen consisting of skincare and, where applicable, medications should be implemented from the beginning or even before oncological therapy to help minimize the incidence of AEs. Reactive treatment is necessary to avoid unnecessary treatment modifications. Interdisciplinary collaboration between dermatologists, oncologists, and other professionals as well as further research in this field is necessary since the current strategies for skin toxicity management are still evolving.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Medical Writing/Editorial Assistance

No outside medical writing assistance has been received during the writing of this manuscript.

Author Contributions

All authors (Piotr Janicki, Anna Makowska, Anna Jakubczyk-Słabicka, Renata Zaucha, Wioletta Barańska-Rybak, Witold Owczarek and Magdalena Górska-Ponikowska) contributed to the study conception and design. Material preparation, data collection and analysis were performed by Piotr Janicki, Anna Makowska and Anna Jakubczyk-Słabicka. The first draft of the manuscript was written by Piotr Janicki and Anna Makowska. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Funding

Magdalena Górska-Ponikowska kindly acknowledges support from ST46 funding (Medical University of Gdansk, Gdansk, Poland). The rapid service fee was funded by Medical University of Gdansk.

Data Availability

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

Declarations

Conflict of Interest

Piotr Janicki, Anna Makowska, Anna Jakubczyk-Słabicka, Renata Zaucha, Wioletta Barańska-Rybak, Witold Owczarek and Magdalena Górska-Ponikowska declare no conflicts of interest.

Ethical Approval

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

References

1. Gao C Wang W Liu T Li X Yu Y Wu J Annual review of EGFR inhibitors in 2024 Eur J Med Chem 2025 292 117677 10.1016/j.ejmech.2025.117677 40328037 Gao C, Wang W, Liu T, Li X, Yu Y, Wu J. Annual review of EGFR inhibitors in 2024. Eur J Med Chem. 2025;292:117677. 10.1016/j.ejmech.2025.117677. 40328037 10.1016/j.ejmech.2025.117677

2. Plachouri K-M Florou V Georgiou V Georgiou S Cutaneous side effects of modern targeted therapy and immunotherapy in patients with dermatological malignancies Cancers 2023 15 12 3126 10.3390/cancers15123126 37370736 PMC10296313 Plachouri K-M, Florou V, Georgiou V, Georgiou S. Cutaneous side effects of modern targeted therapy and immunotherapy in patients with dermatological malignancies. Cancers. 2023;15(12):3126. 37370736 10.3390/cancers15123126 PMC10296313

3. Haynes D Morgan EE Chu EY Cutaneous adverse reactions resulting from targeted cancer therapies: histopathologic and clinical findings Hum Pathol 2023 140 129 143 10.1016/j.humpath.2023.04.014 37146945 Haynes D, Morgan EE, Chu EY. Cutaneous adverse reactions resulting from targeted cancer therapies: histopathologic and clinical findings. Hum Pathol. 2023;140:129–43. 10.1016/j.humpath.2023.04.014. 37146945 10.1016/j.humpath.2023.04.014

4. Feldman JL Cho BC Li W Dermatologic prophylaxis and impact on patient-reported outcomes in first-line EGFR -mutant advanced NSCLC treated with amivantamab plus lazertinib: results from the phase 2 COCOON trial J Clin Oncol 2025 43 16_suppl 8641 8641 10.1200/JCO.2025.43.16_suppl.8641 Feldman JL, Cho BC, Li W, et al. Dermatologic prophylaxis and impact on patient-reported outcomes in first-line EGFR -mutant advanced NSCLC treated with amivantamab plus lazertinib: results from the phase 2 COCOON trial. J Clin Oncol. 2025;43(16_suppl):8641–8641. 10.1200/JCO.2025.43.16_suppl.8641.

5. Yuan C Wang B Acneiform eruption induced by molecularly targeted agents in antineoplastic therapy: a review J Cosmet Dermatol 2023 22 8 2150 2157 10.1111/jocd.15704 36924348 Yuan C, Wang B. Acneiform eruption induced by molecularly targeted agents in antineoplastic therapy: a review. J Cosmet Dermatol. 2023;22(8):2150–7. 10.1111/jocd.15704. 36924348 10.1111/jocd.15704

6. Dan H Jiang Q Jia X Qi G Zong D Li Z Dermatologic toxicities in epidermal growth factor receptor: a comprehensive pharmacovigilance study from 2013 to 2023 Front Med 2024 10.3389/fmed.2023.1283807 PMC10848916 38327269 Dan H, Jiang Q, Jia X, Qi G, Zong D, Li Z. Dermatologic toxicities in epidermal growth factor receptor: a comprehensive pharmacovigilance study from 2013 to 2023. Front Med. 2024. 10.3389/fmed.2023.1283807. 10.3389/fmed.2023.1283807 PMC10848916 38327269

7. Ensslin CJ Rosen AC Wu S Lacouture ME Pruritus in patients treated with targeted cancer therapies: systematic review and meta-analysis J Am Acad Dermatol 2013 69 5 708 720 10.1016/j.jaad.2013.06.038 23981682 PMC4181350 Ensslin CJ, Rosen AC, Wu S, Lacouture ME. Pruritus in patients treated with targeted cancer therapies: systematic review and meta-analysis. J Am Acad Dermatol. 2013;69(5):708–20. 10.1016/j.jaad.2013.06.038. 23981682 10.1016/j.jaad.2013.06.038 PMC4181350

8. Petrelli F Borgonovo K Cabiddu M Lonati V Barni S Relationship between skin rash and outcome in non-small-cell lung cancer patients treated with anti-EGFR tyrosine kinase inhibitors: a literature-based meta-analysis of 24 trials Lung Cancer 2012 78 1 8 15 10.1016/j.lungcan.2012.06.009 22795701 Petrelli F, Borgonovo K, Cabiddu M, Lonati V, Barni S. Relationship between skin rash and outcome in non-small-cell lung cancer patients treated with anti-EGFR tyrosine kinase inhibitors: a literature-based meta-analysis of 24 trials. Lung Cancer. 2012;78(1):8–15. 10.1016/j.lungcan.2012.06.009. 22795701 10.1016/j.lungcan.2012.06.009

9. Busam KJ Capodieci P Motzer R Kiehn T Phelan D Halpern AC Cutaneous side-effects in cancer patients treated with the antiepidermal growth factor receptor antibody C225 Br J Dermatol 2001 144 6 1169 1176 10.1046/j.1365-2133.2001.04226.x 11422037 Busam KJ, Capodieci P, Motzer R, Kiehn T, Phelan D, Halpern AC. Cutaneous side-effects in cancer patients treated with the antiepidermal growth factor receptor antibody C225. Br J Dermatol. 2001;144(6):1169–76. 10.1046/j.1365-2133.2001.04226.x. 11422037 10.1046/j.1365-2133.2001.04226.x

10. Matos LV Pissarra A Malheiro M Plácido AN Trichomegaly of the eyelashes induced by the epidermal growth factor receptor inhibitor cetuximab in the treatment of metastatic colorectal cancer BMJ Case Rep 2019 12 4 e228968 10.1136/bcr-2018-228968 31040141 PMC6506099 Matos LV, Pissarra A, Malheiro M, Plácido AN. Trichomegaly of the eyelashes induced by the epidermal growth factor receptor inhibitor cetuximab in the treatment of metastatic colorectal cancer. BMJ Case Rep. 2019;12(4):e228968. 10.1136/bcr-2018-228968. 31040141 10.1136/bcr-2018-228968 PMC6506099

11. Wollina U Systemic drug-induced chronic paronychia and periungual pyogenic granuloma Indian Dermatol Online J 2018 9 5 293 10.4103/idoj.IDOJ_133_18 30258794 PMC6137670 Wollina U. Systemic drug-induced chronic paronychia and periungual pyogenic granuloma. Indian Dermatol Online J. 2018;9(5):293. 10.4103/idoj.IDOJ_133_18. 30258794 10.4103/idoj.IDOJ_133_18 PMC6137670

12. Lee JS Woo J Kim TM Kim N Keam B Jo SJ Skin toxicities induced by epidermal growth factor receptor tyrosine kinase inhibitors and their influence on treatment adjustments in lung cancer patients Acta Derm Venereol 2024 104 adv40555 10.2340/actadv.v104.40555 39192813 PMC11370047 Lee JS, Woo J, Kim TM, Kim N, Keam B, Jo SJ. Skin toxicities induced by epidermal growth factor receptor tyrosine kinase inhibitors and their influence on treatment adjustments in lung cancer patients. Acta Derm Venereol. 2024;104:adv40555. 10.2340/actadv.v104.40555. 39192813 10.2340/actadv.v104.40555 PMC11370047

13. Arana I Riew GJ Rock A Nambudiri VE Modi B Shi CR Cutaneous toxicities associated with epidermal growth factor receptor and mesenchymal epithelial transition factor dual blockade via bispecific antibody amivantamab J Am Acad Dermatol 2025 92 6 1404 1406 10.1016/j.jaad.2025.02.007 39922286 Arana I, Riew GJ, Rock A, Nambudiri VE, Modi B, Shi CR. Cutaneous toxicities associated with epidermal growth factor receptor and mesenchymal epithelial transition factor dual blockade via bispecific antibody amivantamab. J Am Acad Dermatol. 2025;92(6):1404–6. 10.1016/j.jaad.2025.02.007. 39922286 10.1016/j.jaad.2025.02.007

14. Starace M Rapparini L Cedirian S Erosive pustular dermatosis of the scalp due to EGFR inhibitors: a multicentric study by EADV task force of ‘Dermatology for Cancer Patients’ J Eur Acad Dermatol Venereol 2025 39 9 e745 e749 10.1111/jdv.20569 39898721 Starace M, Rapparini L, Cedirian S, et al. Erosive pustular dermatosis of the scalp due to EGFR inhibitors: A multicentric study by EADV task force of 'Dermatology for Cancer Patients'. J Eur Acad Dermatol Venereol. 2025;39(9):e745-e749. 10.1111/jdv.20569 39898721 10.1111/jdv.20569

15. Qian J Wan J Yao Q Cutaneous adverse events associated with BRAF and MEK inhibitors: a systematic review and meta-analysis Front Pharmacol 2024 15 1457226 10.3389/fphar.2024.1457226 39776585 PMC11703664 Qian J, Wan J, Yao Q, et al. Cutaneous adverse events associated with BRAF and MEK inhibitors: a systematic review and meta-analysis. Front Pharmacol. 2024;15:1457226. 10.3389/fphar.2024.1457226. 39776585 10.3389/fphar.2024.1457226 PMC11703664

16. Garutti M Bergnach M Polesel J Palmero L Pizzichetta MA Puglisi F BRAF and MEK inhibitors and their toxicities: a meta-analysis Cancers (Basel) 2022 15 1 141 10.3390/cancers15010141 36612138 PMC9818023 Garutti M, Bergnach M, Polesel J, Palmero L, Pizzichetta MA, Puglisi F. BRAF and MEK inhibitors and their toxicities: a meta-analysis. Cancers (Basel). 2022;15(1):141. 10.3390/cancers15010141. 36612138 10.3390/cancers15010141 PMC9818023

17. Peng L Wang Y Hong Y Incidence and relative risk of cutaneous squamous cell carcinoma with single-agent BRAF inhibitor and dual BRAF/MEK inhibitors in cancer patients: a meta-analysis Oncotarget 2017 8 47 83280 83291 10.18632/oncotarget.21059 29137342 PMC5669968 Peng L, Wang Y, Hong Y, et al. Incidence and relative risk of cutaneous squamous cell carcinoma with single-agent BRAF inhibitor and dual BRAF/MEK inhibitors in cancer patients: a meta-analysis. Oncotarget. 2017;8(47):83280–91. 10.18632/oncotarget.21059. 29137342 10.18632/oncotarget.21059 PMC5669968

18. Lacouture M Sibaud V Toxic side effects of targeted therapies and immunotherapies affecting the skin, oral mucosa, hair, and nails Am J Clin Dermatol 2018 19 S1 31 39 10.1007/s40257-018-0384-3 30374901 PMC6244569 Lacouture M, Sibaud V. Toxic side effects of targeted therapies and immunotherapies affecting the skin, oral mucosa, hair, and nails. Am J Clin Dermatol. 2018;19(S1):31–9. 10.1007/s40257-018-0384-3. 30374901 10.1007/s40257-018-0384-3 PMC6244569

19. Schlam I Swain SM HER2-positive breast cancer and tyrosine kinase inhibitors: the time is now NPJ Breast Cancer 2021 7 1 56 10.1038/s41523-021-00265-1 34016991 PMC8137941 Schlam I, Swain SM. HER2-positive breast cancer and tyrosine kinase inhibitors: the time is now. NPJ Breast Cancer. 2021;7(1):56. 10.1038/s41523-021-00265-1. 34016991 10.1038/s41523-021-00265-1 PMC8137941

20. Laux I Jain A Singh S Agus DB Epidermal growth factor receptor dimerization status determines skin toxicity to HER-kinase targeted therapies Br J Cancer 2006 94 1 85 92 10.1038/sj.bjc.6602875 16306877 PMC2361091 Laux I, Jain A, Singh S, Agus DB. Epidermal growth factor receptor dimerization status determines skin toxicity to HER-kinase targeted therapies. Br J Cancer. 2006;94(1):85–92. 10.1038/sj.bjc.6602875. 16306877 10.1038/sj.bjc.6602875 PMC2361091

21. Lacouture ME Laabs SM Koehler M Analysis of dermatologic events in patients with cancer treated with lapatinib Breast Cancer Res Treat 2009 114 3 485 493 10.1007/s10549-008-0020-7 18600445 Lacouture ME, Laabs SM, Koehler M, et al. Analysis of dermatologic events in patients with cancer treated with lapatinib. Breast Cancer Res Treat. 2009;114(3):485–93. 10.1007/s10549-008-0020-7. 18600445 10.1007/s10549-008-0020-7

22. Nakano K Komatsu K Kubo T Hand-foot skin reaction is associated with the clinical outcome in patients with metastatic renal cell carcinoma treated with sorafenib Jpn J Clin Oncol 2013 43 10 1023 1029 10.1093/jjco/hyt110 23956442 Nakano K, Komatsu K, Kubo T, et al. Hand-foot skin reaction is associated with the clinical outcome in patients with metastatic renal cell carcinoma treated with sorafenib. Jpn J Clin Oncol. 2013;43(10):1023–9. 10.1093/jjco/hyt110. 23956442 10.1093/jjco/hyt110

23. Nagore E Insa A Sanmartn O Antineoplastic therapy induced palmar plantar erythrodysesthesia (hand–foot) syndrome Am J Clin Dermatol 2000 1 4 225 234 10.2165/00128071-200001040-00004 11702367 Nagore E, Insa A, Sanmartn O. Antineoplastic therapy induced palmar plantar erythrodysesthesia (hand–foot) syndrome. Am J Clin Dermatol. 2000;1(4):225–34. 10.2165/00128071-200001040-00004. 11702367 10.2165/00128071-200001040-00004

24. Sodergren SC Copson E White A Systematic review of the side effects associated with anti-HER2-targeted therapies used in the treatment of breast cancer, on behalf of the EORTC quality of life group Target Oncol 2016 11 3 277 292 10.1007/s11523-015-0409-2 26677846 Sodergren SC, Copson E, White A, et al. Systematic review of the side effects associated with anti-HER2-targeted therapies used in the treatment of breast cancer, on behalf of the EORTC quality of life group. Target Oncol. 2016;11(3):277–92. 10.1007/s11523-015-0409-2. 26677846 10.1007/s11523-015-0409-2

25. Raschi E Fusaroli M La Placa M Skin toxicities with cyclin-dependent kinase 4/6 inhibitors in breast cancer: signals from disproportionality analysis of the FDA adverse event reporting system Am J Clin Dermatol 2022 23 2 247 255 10.1007/s40257-021-00645-0 34699032 Raschi E, Fusaroli M, La Placa M, et al. Skin toxicities with cyclin-dependent kinase 4/6 inhibitors in breast cancer: signals from disproportionality analysis of the FDA adverse event reporting system. Am J Clin Dermatol. 2022;23(2):247–55. 10.1007/s40257-021-00645-0. 34699032 10.1007/s40257-021-00645-0

26. Chawla S Hill A Fearfield L Johnston S Parton M Heelan K Cutaneous toxicities occurring during palbociclib (CDK4/6 inhibitor) and endocrine therapy in patients with advanced breast cancer: a single-centre experience Breast Cancer Res Treat 2021 188 2 535 545 10.1007/s10549-021-06169-9 33683521 Chawla S, Hill A, Fearfield L, Johnston S, Parton M, Heelan K. Cutaneous toxicities occurring during palbociclib (CDK4/6 inhibitor) and endocrine therapy in patients with advanced breast cancer: a single-centre experience. Breast Cancer Res Treat. 2021;188(2):535–45. 10.1007/s10549-021-06169-9. 33683521 10.1007/s10549-021-06169-9

27. Sollena P Vasiliki N Kotteas E Cyclin-dependent kinase 4/6 inhibitors and dermatologic adverse events: results from the EADV task force ‘dermatology for cancer patients’ international study Cancers 2023 15 14 3658 10.3390/cancers15143658 37509319 PMC10377938 Sollena P, Vasiliki N, Kotteas E, et al. Cyclin-dependent kinase 4/6 inhibitors and dermatologic adverse events: results from the EADV task force ‘dermatology for cancer patients’ international study. Cancers. 2023;15(14):3658. 10.3390/cancers15143658. 37509319 10.3390/cancers15143658 PMC10377938

28. Sibaud V Sollena P Dermatologic toxicities to inhibitors of cyclin-dependent kinases CDK 4 and 6: an updated review for clinical practice Ann Dermatol Venereol 2023 150 3 208 212 10.1016/j.annder.2022.11.013 37586898 Sibaud V, Sollena P. Dermatologic toxicities to inhibitors of cyclin-dependent kinases CDK 4 and 6: an updated review for clinical practice. Ann Dermatol Venereol. 2023;150(3):208–12. 10.1016/j.annder.2022.11.013. 37586898 10.1016/j.annder.2022.11.013

29. Silvestri M Cristaudo A Morrone A Emerging skin toxicities in patients with breast cancer treated with new cyclin-dependent kinase 4/6 inhibitors: a systematic review Drug Saf 2021 44 7 725 732 10.1007/s40264-021-01071-1 33959899 Silvestri M, Cristaudo A, Morrone A, et al. Emerging skin toxicities in patients with breast cancer treated with new cyclin-dependent kinase 4/6 inhibitors: a systematic review. Drug Saf. 2021;44(7):725–32. 10.1007/s40264-021-01071-1. 33959899 10.1007/s40264-021-01071-1

30. Sledge GW Toi M Neven P MONARCH 2: abemaciclib in combination with fulvestrant in women with HR+/HER2− advanced breast cancer who had progressed while receiving endocrine therapy J Clin Oncol 2017 35 25 2875 2884 10.1200/JCO.2017.73.7585 28580882 Sledge GW, Toi M, Neven P, et al. MONARCH 2: abemaciclib in combination with fulvestrant in women with HR+/HER2− advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol. 2017;35(25):2875–84. 10.1200/JCO.2017.73.7585. 28580882 10.1200/JCO.2017.73.7585

31. Hortobagyi GN Stemmer SM Burris HA Ribociclib as first-line therapy for HR-positive, advanced breast cancer N Engl J Med 2016 375 18 1738 1748 10.1056/NEJMoa1609709 27717303 Hortobagyi GN, Stemmer SM, Burris HA, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med. 2016;375(18):1738–48. 10.1056/NEJMoa1609709. 27717303 10.1056/NEJMoa1609709

32. Preetham P Sudha S Kabilan N Dermatoses induced by multikinase inhibitors: a case report Our Dermatol Online 2023 10.7241/ourd.20232.13 Preetham P, Sudha S, Kabilan N. Dermatoses induced by multikinase inhibitors: a case report. Our Dermatol Online. 2023. 10.7241/ourd.20232.13.

33. Massey PR Okman JS Wilkerson J Cowen EW Tyrosine kinase inhibitors directed against the vascular endothelial growth factor receptor (VEGFR) have distinct cutaneous toxicity profiles: a meta-analysis and review of the literature Support Care Cancer 2015 23 6 1827 1835 10.1007/s00520-014-2520-9 25471178 PMC4414682 Massey PR, Okman JS, Wilkerson J, Cowen EW. Tyrosine kinase inhibitors directed against the vascular endothelial growth factor receptor (VEGFR) have distinct cutaneous toxicity profiles: a meta-analysis and review of the literature. Support Care Cancer. 2015;23(6):1827–35. 10.1007/s00520-014-2520-9. 25471178 10.1007/s00520-014-2520-9 PMC4414682

34. Andrae J Gallini R Betsholtz C Role of platelet-derived growth factors in physiology and medicine Genes Dev 2008 22 10 1276 1312 10.1101/gad.1653708 18483217 PMC2732412 Andrae J, Gallini R, Betsholtz C. Role of platelet-derived growth factors in physiology and medicine. Genes Dev. 2008;22(10):1276–312. 10.1101/gad.1653708. 18483217 10.1101/gad.1653708 PMC2732412

35. Breccia M Carmosino I Russo E Morano SG Latagliata R Alimena G Early and tardive skin adverse events in chronic myeloid leukaemia patients treated with imatinib Eur J Haematol 2005 74 2 121 123 10.1111/j.1600-0609.2004.00351.x 15654902 Breccia M, Carmosino I, Russo E, Morano SG, Latagliata R, Alimena G. Early and tardive skin adverse events in chronic myeloid leukaemia patients treated with imatinib. Eur J Haematol. 2005;74(2):121–3. 10.1111/j.1600-0609.2004.00351.x. 15654902 10.1111/j.1600-0609.2004.00351.x

36. Kuraishi N Nagai Y Hasegawa M Ishikawa O Lichenoid drug eruption with palmoplantar hyperkeratosis due to imatinib mesylate: a case report and a review of the literature Acta Derm Venereol 2010 90 1 73 76 10.2340/00015555-0758 20107730 Kuraishi N, Nagai Y, Hasegawa M, Ishikawa O. Lichenoid drug eruption with palmoplantar hyperkeratosis due to imatinib mesylate: a case report and a review of the literature. Acta Derm Venereol. 2010;90(1):73–6. 10.2340/00015555-0758. 20107730 10.2340/00015555-0758

37. Dessinioti C Antoniou C Stratigos AJ From basal cell carcinoma morphogenesis to the alopecia induced by hedgehog inhibitors: connecting the dots Br J Dermatol 2017 177 6 1485 1494 10.1111/bjd.15738 28626889 Dessinioti C, Antoniou C, Stratigos AJ. From basal cell carcinoma morphogenesis to the alopecia induced by hedgehog inhibitors: connecting the dots. Br J Dermatol. 2017;177(6):1485–94. 10.1111/bjd.15738. 28626889 10.1111/bjd.15738

38. Farberg AS Portela D Sharma D Kheterpal M Evaluation of the tolerability of hedgehog pathway inhibitors in the treatment of advanced basal cell carcinoma: a narrative review of treatment strategies Am J Clin Dermatol 2024 25 5 779 794 10.1007/s40257-024-00870-3 38896403 PMC11358199 Farberg AS, Portela D, Sharma D, Kheterpal M. Evaluation of the tolerability of hedgehog pathway inhibitors in the treatment of advanced basal cell carcinoma: a narrative review of treatment strategies. Am J Clin Dermatol. 2024;25(5):779–94. 10.1007/s40257-024-00870-3. 38896403 10.1007/s40257-024-00870-3 PMC11358199

39. Nguyen A Xie P Litvinov IV Lefrançois P Efficacy and safety of sonic hedgehog inhibitors in basal cell carcinomas: an updated systematic review and meta-analysis (2009–2022) Am J Clin Dermatol 2023 24 3 359 374 10.1007/s40257-023-00763-x 36795228 Nguyen A, Xie P, Litvinov IV, Lefrançois P. Efficacy and safety of sonic hedgehog inhibitors in basal cell carcinomas: an updated systematic review and meta-analysis (2009–2022). Am J Clin Dermatol. 2023;24(3):359–74. 10.1007/s40257-023-00763-x. 36795228 10.1007/s40257-023-00763-x

40. Herms F Djermane M Beylot-Barry M Comparison of the tolerability and safety of hedgehog inhibitors in real-life: a cohort of 330 patients with locally advanced basal cell carcinoma. J Clin Oncol 2025 43 16_suppl 9583 9583 10.1200/JCO.2025.43.16_suppl.9583 Herms F, Djermane M, Beylot-Barry M, et al. Comparison of the tolerability and safety of hedgehog inhibitors in real-life: a cohort of 330 patients with locally advanced basal cell carcinoma. J Clin Oncol. 2025;43(16_suppl):9583–9583. 10.1200/JCO.2025.43.16_suppl.9583.

41. Kang S Kim S-B Toxicities and management strategies of emerging antibody–drug conjugates in breast cancer Ther Adv Med Oncol 2025 10.1177/17588359251324889 40151551 PMC11946287 Kang S, Kim S-B. Toxicities and management strategies of emerging antibody–drug conjugates in breast cancer. Ther Adv Med Oncol. 2025. 10.1177/17588359251324889. 40151551 10.1177/17588359251324889 PMC11946287

42. Tijink BM Buter J de Bree R A phase I dose escalation study with anti-CD44v6 bivatuzumab mertansine in patients with incurable squamous cell carcinoma of the head and neck or esophagus Clin Cancer Res 2006 12 20 6064 6072 10.1158/1078-0432.CCR-06-0910 17062682 Tijink BM, Buter J, de Bree R, et al. A phase I dose escalation study with anti-CD44v6 bivatuzumab mertansine in patients with incurable squamous cell carcinoma of the head and neck or esophagus. Clin Cancer Res. 2006;12(20):6064–72. 10.1158/1078-0432.CCR-06-0910. 17062682 10.1158/1078-0432.CCR-06-0910

43. Riechelmann H Sauter A Golze W Phase I trial with the CD44v6-targeting immunoconjugate bivatuzumab mertansine in head and neck squamous cell carcinoma Oral Oncol 2008 44 9 823 829 10.1016/j.oraloncology.2007.10.009 18203652 Riechelmann H, Sauter A, Golze W, et al. Phase I trial with the CD44v6-targeting immunoconjugate bivatuzumab mertansine in head and neck squamous cell carcinoma. Oral Oncol. 2008;44(9):823–9. 10.1016/j.oraloncology.2007.10.009. 18203652 10.1016/j.oraloncology.2007.10.009

44. D’Arienzo A Verrazzo A Pagliuca M Toxicity profile of antibody-drug conjugates in breast cancer: practical considerations EClinicalMedicine 2023 62 102113 10.1016/j.eclinm.2023.102113 37554126 PMC10404866 D’Arienzo A, Verrazzo A, Pagliuca M, et al. Toxicity profile of antibody-drug conjugates in breast cancer: practical considerations. EClinicalMedicine. 2023;62:102113. 10.1016/j.eclinm.2023.102113. 37554126 10.1016/j.eclinm.2023.102113 PMC10404866

45. Gazzoni G Michelon I Vilbert M Enfortumab vedotin-related skin toxicities in patients with urothelial carcinoma: a systematic review and meta-analysis Urol Oncol Semin Orig Investig 2025 43 10 595.e1 595.e11 10.1016/j.urolonc.2025.05.016 40592676 Gazzoni G, Michelon I, Vilbert M, et al. Enfortumab vedotin-related skin toxicities in patients with urothelial carcinoma: a systematic review and meta-analysis. Urol Oncol Semin Orig Investig. 2025;43(10):595.e1-595.e11. 10.1016/j.urolonc.2025.05.016. 10.1016/j.urolonc.2025.05.016 40592676

46. Rosenberg JE O’Donnell PH Balar AV Pivotal trial of enfortumab vedotin in urothelial carcinoma after platinum and anti-programmed death 1/programmed death ligand 1 therapy J Clin Oncol 2019 37 29 2592 2600 10.1200/JCO.19.01140 31356140 PMC6784850 Rosenberg JE, O’Donnell PH, Balar AV, et al. Pivotal trial of enfortumab vedotin in urothelial carcinoma after platinum and anti-programmed death 1/programmed death ligand 1 therapy. J Clin Oncol. 2019;37(29):2592–600. 10.1200/JCO.19.01140. 31356140 10.1200/JCO.19.01140 PMC6784850

47. Oh Y Bang A Kurtansky N Khan N Pulitzer M Noor S Dermatologic adverse events of brentuximab vedotin: characteristics, management, and their relationship with dose regimen J Clin Oncol 2021 39 15_suppl 3049 3049 10.1200/JCO.2021.39.15_suppl.3049 Oh Y, Bang A, Kurtansky N, Khan N, Pulitzer M, Noor S. Dermatologic adverse events of brentuximab vedotin: characteristics, management, and their relationship with dose regimen. J Clin Oncol. 2021;39(15_suppl):3049–3049. 10.1200/JCO.2021.39.15_suppl.3049.

48. Bardia A Mayer IA Vahdat LT Sacituzumab govitecan-hziy in refractory metastatic triple-negative breast cancer N Engl J Med 2019 380 8 741 751 10.1056/NEJMoa1814213 30786188 Bardia A, Mayer IA, Vahdat LT, et al. Sacituzumab govitecan-hziy in refractory metastatic triple-negative breast cancer. N Engl J Med. 2019;380(8):741–51. 10.1056/NEJMoa1814213. 30786188 10.1056/NEJMoa1814213

49. Bardia A Hurvitz SA Tolaney SM Sacituzumab govitecan in metastatic triple-negative breast cancer N Engl J Med 2021 384 16 1529 1541 10.1056/NEJMoa2028485 33882206 Bardia A, Hurvitz SA, Tolaney SM, et al. Sacituzumab govitecan in metastatic triple-negative breast cancer. N Engl J Med. 2021;384(16):1529–41. 10.1056/NEJMoa2028485. 33882206 10.1056/NEJMoa2028485

50. Reinisch M Bruzas S Spoenlein J Safety and effectiveness of sacituzumab govitecan in patients with metastatic triple-negative breast cancer in real-world settings: first observations from an interdisciplinary breast cancer centre in Germany Ther Adv Med Oncol 2023 10.1177/17588359231200454 37789989 PMC10542232 Reinisch M, Bruzas S, Spoenlein J, et al. Safety and effectiveness of sacituzumab govitecan in patients with metastatic triple-negative breast cancer in real-world settings: first observations from an interdisciplinary breast cancer centre in Germany. Ther Adv Med Oncol. 2023. 10.1177/17588359231200454. 37789989 10.1177/17588359231200454 PMC10542232

51. Lacouture ME Sibaud V Anadkat MJ Dermatologic adverse events associated with selective fibroblast growth factor receptor inhibitors: overview, prevention, and management guidelines Oncologist 2021 26 2 e316 e326 10.1002/onco.13552 33021006 PMC7873330 Lacouture ME, Sibaud V, Anadkat MJ, et al. Dermatologic adverse events associated with selective fibroblast growth factor receptor inhibitors: overview, prevention, and management guidelines. Oncologist. 2021;26(2):e316–26. 10.1002/onco.13552. 33021006 10.1002/onco.13552 PMC7873330

52. Grochot R Joshi K Cammarota A Safety and activity of fibroblast growth factor receptor inhibitors in advanced malignancies: a pooled analysis of early-phase clinical trials JCO Precis Oncol 2025 10.1200/PO-24-00896 40239140 Grochot R, Joshi K, Cammarota A, et al. Safety and activity of fibroblast growth factor receptor inhibitors in advanced malignancies: a pooled analysis of early-phase clinical trials. JCO Precis Oncol. 2025. 10.1200/PO-24-00896. 40239140 10.1200/PO-24-00896

53. Subbiah V Verstovsek S Clinical development and management of adverse events associated with FGFR inhibitors Cell Rep Med 2023 4 10 101204 10.1016/j.xcrm.2023.101204 37757826 PMC10591034 Subbiah V, Verstovsek S. Clinical development and management of adverse events associated with FGFR inhibitors. Cell Rep Med. 2023;4(10):101204. 10.1016/j.xcrm.2023.101204. 37757826 10.1016/j.xcrm.2023.101204 PMC10591034

54. Ishida T Inagaki H Utsunomiya A CXC chemokine receptor 3 and CC chemokine receptor 4 expression in T-cell and NK-cell lymphomas with special reference to clinicopathological significance for peripheral T-cell lymphoma, unspecified Clin Cancer Res 2004 10 16 5494 5500 10.1158/1078-0432.CCR-04-0371 15328188 Ishida T, Inagaki H, Utsunomiya A, et al. CXC chemokine receptor 3 and CC chemokine receptor 4 expression in T-cell and NK-cell lymphomas with special reference to clinicopathological significance for peripheral T-cell lymphoma, unspecified. Clin Cancer Res. 2004;10(16):5494–500. 10.1158/1078-0432.CCR-04-0371. 15328188 10.1158/1078-0432.CCR-04-0371

55. Ferenczi K Fuhlbrigge RC Kupper TS Pinkus JL Pinkus GS Increased CCR4 expression in cutaneous T cell lymphoma J Invest Dermatol 2002 119 6 1405 1410 10.1046/j.1523-1747.2002.19610.x 12485447 Ferenczi K, Fuhlbrigge RC, Kupper TS, Pinkus JL, Pinkus GS. Increased CCR4 expression in cutaneous T cell lymphoma. J Invest Dermatol. 2002;119(6):1405–10. 10.1046/j.1523-1747.2002.19610.x. 12485447 10.1046/j.1523-1747.2002.19610.x

56. Yoshie O CCR4 as a therapeutic target for cancer immunotherapy Cancers 2021 13 21 5542 10.3390/cancers13215542 34771703 PMC8583476 Yoshie O. CCR4 as a therapeutic target for cancer immunotherapy. Cancers. 2021;13(21):5542. 10.3390/cancers13215542. 34771703 10.3390/cancers13215542 PMC8583476

57. Saito M Ishii T Urakawa I Robust CD8+ T-cell proliferation and diversification after mogamulizumab in patients with adult T-cell leukemia-lymphoma Blood Adv 2020 4 10 2180 2191 10.1182/bloodadvances.2020001641 32433748 PMC7252545 Saito M, Ishii T, Urakawa I, et al. Robust CD8+ T-cell proliferation and diversification after mogamulizumab in patients with adult T-cell leukemia-lymphoma. Blood Adv. 2020;4(10):2180–91. 10.1182/bloodadvances.2020001641. 32433748 10.1182/bloodadvances.2020001641 PMC7252545

58. Ogura M Ishida T Hatake K Multicenter phase II study of mogamulizumab (KW-0761), a defucosylated anti-CC chemokine receptor 4 antibody, in patients with relapsed peripheral T-cell lymphoma and cutaneous T-cell lymphoma J Clin Oncol 2014 32 11 1157 1163 10.1200/JCO.2013.52.0924 24616310 Ogura M, Ishida T, Hatake K, et al. Multicenter phase II study of mogamulizumab (KW-0761), a defucosylated anti-CC chemokine receptor 4 antibody, in patients with relapsed peripheral T-cell lymphoma and cutaneous T-cell lymphoma. J Clin Oncol. 2014;32(11):1157–63. 10.1200/JCO.2013.52.0924. 24616310 10.1200/JCO.2013.52.0924

59. Ishida T Joh T Uike N Defucosylated anti-CCR4 monoclonal antibody (KW-0761) for relapsed adult T-cell leukemia-lymphoma: a multicenter phase II study J Clin Oncol 2012 30 8 837 842 10.1200/JCO.2011.37.3472 22312108 Ishida T, Joh T, Uike N, et al. Defucosylated anti-CCR4 monoclonal antibody (KW-0761) for relapsed adult T-cell leukemia-lymphoma: a multicenter phase II study. J Clin Oncol. 2012;30(8):837–42. 10.1200/JCO.2011.37.3472. 22312108 10.1200/JCO.2011.37.3472

60. Algarni AS Ram-Wolff C Bagot M De Masson A Mogamulizumab-induced vitiligo in patients with Sézary syndrome: three cases Eur J Dermatol 2021 31 2 213 216 10.1684/ejd.2021.4002 33814357 Algarni AS, Ram-Wolff C, Bagot M, De Masson A. Mogamulizumab-induced vitiligo in patients with Sézary syndrome: three cases. Eur J Dermatol. 2021;31(2):213–6. 10.1684/ejd.2021.4002. 33814357 10.1684/ejd.2021.4002

61. Hirotsu KE Neal TM Khodadoust MS Clinical characterization of mogamulizumab-associated rash during treatment of mycosis fungoides or Sézary syndrome JAMA Dermatol 2021 157 6 700 10.1001/jamadermatol.2021.0877 33881447 PMC8060888 Hirotsu KE, Neal TM, Khodadoust MS, et al. Clinical characterization of mogamulizumab-associated rash during treatment of mycosis fungoides or Sézary syndrome. JAMA Dermatol. 2021;157(6):700. 10.1001/jamadermatol.2021.0877. 33881447 10.1001/jamadermatol.2021.0877 PMC8060888

62. Yonekura K Kanzaki T Gunshin K Effect of anti-CCR 4 monoclonal antibody (mogamulizumab) on adult T-cell leukemia–lymphoma: cutaneous adverse reactions may predict the prognosis J Dermatol 2014 41 3 239 244 10.1111/1346-8138.12419 24628073 Yonekura K, Kanzaki T, Gunshin K, et al. Effect of anti-CCR 4 monoclonal antibody (mogamulizumab) on adult T-cell leukemia–lymphoma: cutaneous adverse reactions may predict the prognosis. J Dermatol. 2014;41(3):239–44. 10.1111/1346-8138.12419. 24628073 10.1111/1346-8138.12419

63. Tomsitz D Kerl K French LE Heinzerling L Clinical and pathological characterization of tebentafusp-associated skin toxicity: a cohort study with 33 patients J Am Acad Dermatol 2024 91 6 1136 1142 10.1016/j.jaad.2024.08.037 39216820 Tomsitz D, Kerl K, French LE, Heinzerling L. Clinical and pathological characterization of tebentafusp-associated skin toxicity: a cohort study with 33 patients. J Am Acad Dermatol. 2024;91(6):1136–42. 10.1016/j.jaad.2024.08.037. 39216820 10.1016/j.jaad.2024.08.037

64. Middleton MR McAlpine C Woodcock VK Tebentafusp, a TCR/anti-CD3 bispecific fusion protein targeting gp100, potently activated antitumor immune responses in patients with metastatic melanoma Clin Cancer Res 2020 26 22 5869 5878 10.1158/1078-0432.CCR-20-1247 32816891 PMC9210997 Middleton MR, McAlpine C, Woodcock VK, et al. Tebentafusp, a TCR/anti-CD3 bispecific fusion protein targeting gp100, potently activated antitumor immune responses in patients with metastatic melanoma. Clin Cancer Res. 2020;26(22):5869–78. 10.1158/1078-0432.CCR-20-1247. 32816891 10.1158/1078-0432.CCR-20-1247 PMC9210997

65. Fahmy LM Schreidah CM McDonnell DE Carvajal RD Magro CM Geskin LJ Cutaneous type IV hypersensitivity reaction following tebentafusp treatment for uveal melanoma Dermatol Online J 2024 10.5070/D329662993 38478664 Fahmy LM, Schreidah CM, McDonnell DE, Carvajal RD, Magro CM, Geskin LJ. Cutaneous type IV hypersensitivity reaction following tebentafusp treatment for uveal melanoma. Dermatol Online J. 2024. 10.5070/D329662993. 38478664 10.5070/D329662993

66. Chari A Minnema MC Berdeja JG Talquetamab, a T-cell-redirecting GPRC5D bispecific antibody for multiple myeloma N Engl J Med 2022 387 24 2232 2244 10.1056/NEJMoa2204591 36507686 Chari A, Minnema MC, Berdeja JG, et al. Talquetamab, a T-cell-redirecting GPRC5D bispecific antibody for multiple myeloma. N Engl J Med. 2022;387(24):2232–44. 10.1056/NEJMoa2204591. 36507686 10.1056/NEJMoa2204591

67. Schinke CD Touzeau C Minnema MC Pivotal phase 2 MonumenTAL-1 results of talquetamab (tal), a GPRC5DxCD3 bispecific antibody (BsAb), for relapsed/refractory multiple myeloma (RRMM) J Clin Oncol 2023 41 16_suppl 8036 8036 10.1200/JCO.2023.41.16_suppl.8036 Schinke CD, Touzeau C, Minnema MC, et al. Pivotal phase 2 MonumenTAL-1 results of talquetamab (tal), a GPRC5DxCD3 bispecific antibody (BsAb), for relapsed/refractory multiple myeloma (RRMM). J Clin Oncol. 2023;41(16_suppl):8036–8036. 10.1200/JCO.2023.41.16_suppl.8036.

68. Rodriguez-Otero P van de Donk NWCJ Pillarisetti K GPRC5D as a novel target for the treatment of multiple myeloma: a narrative review Blood Cancer J 2024 14 1 24 10.1038/s41408-023-00966-9 38307865 PMC10837198 Rodriguez-Otero P, van de Donk NWCJ, Pillarisetti K, et al. GPRC5D as a novel target for the treatment of multiple myeloma: a narrative review. Blood Cancer J. 2024;14(1):24. 10.1038/s41408-023-00966-9. 38307865 10.1038/s41408-023-00966-9 PMC10837198

69. US Department of Health and Human Services Common terminology criteria for adverse events (CTCAE) v5.0 Cancer Ther Eval Progr 2017 155 90 92 US Department of Health and Human Services. Common terminology criteria for adverse events (CTCAE) v5.0. Cancer Ther Eval Progr. 2017;155:90–2.

70. Apalla Z Nikolaou V Fattore D European recommendations for management of immune checkpoint inhibitors-derived dermatologic adverse events. The EADV task force ‘Dermatology for cancer patients’ position statement J Eur Acad Dermatol Venereol 2022 36 3 332 350 10.1111/jdv.17855 34910332 Apalla Z, Nikolaou V, Fattore D, et al. European recommendations for management of immune checkpoint inhibitors-derived dermatologic adverse events. The EADV task force ‘Dermatology for cancer patients’ position statement. J Eur Acad Dermatol Venereol. 2022;36(3):332–50. 10.1111/jdv.17855. 34910332 10.1111/jdv.17855

71. Hassel JC Kripp M Al-Batran S Hofheinz R-D Treatment of epidermal growth factor receptor antagonist-induced skin rash: results of a survey among German oncologists Onkologie 2010 33 3 94 98 10.1159/000277656 20215799 Hassel JC, Kripp M, Al-Batran S, Hofheinz R-D. Treatment of epidermal growth factor receptor antagonist-induced skin rash: results of a survey among German oncologists. Onkologie. 2010;33(3):94–8. 10.1159/000277656. 20215799 10.1159/000277656

72. Barrios DM Phillips GS Geisler AN IgE blockade with omalizumab reduces pruritus related to immune checkpoint inhibitors and anti-HER2 therapies Ann Oncol 2021 32 6 736 745 10.1016/j.annonc.2021.02.016 33667669 PMC9282165 Barrios DM, Phillips GS, Geisler AN, et al. IgE blockade with omalizumab reduces pruritus related to immune checkpoint inhibitors and anti-HER2 therapies. Ann Oncol. 2021;32(6):736–45. 10.1016/j.annonc.2021.02.016. 33667669 10.1016/j.annonc.2021.02.016 PMC9282165

73. Kuo AM-S Gu S Stoll J Management of immune-related cutaneous adverse events with dupilumab J Immunother Cancer 2023 11 6 e007324 10.1136/jitc-2023-007324 37270183 PMC10255229 Kuo AMS, Gu S, Stoll J, et al. Management of immune-related cutaneous adverse events with dupilumab. J Immunother Cancer. 2023;11(6):e007324. 10.1136/jitc-2023-007324. 37270183 10.1136/jitc-2023-007324 PMC10255229

74. Geisler AN Phillips GS Barrios DM Immune checkpoint inhibitor-related dermatologic adverse events J Am Acad Dermatol 2020 83 5 1255 1268 10.1016/j.jaad.2020.03.132 32454097 PMC7572894 Geisler AN, Phillips GS, Barrios DM, et al. Immune checkpoint inhibitor-related dermatologic adverse events. J Am Acad Dermatol. 2020;83(5):1255–68. 10.1016/j.jaad.2020.03.132. 32454097 10.1016/j.jaad.2020.03.132 PMC7572894

75. Fattore D Apalla Z Freites-Martinez A Prevention and management of cutaneous immune-related adverse events: EADV Task Force statement J Eur Acad Dermatol Venereol 2025 10.1111/jdv.70149 41165224 Fattore D, Apalla Z, Freites-Martinez A, et al. Prevention and management of cutaneous immune-related adverse events: EADV Task Force statement. J Eur Acad Dermatol Venereol. 2025. 10.1111/jdv.70149. 41165224 10.1111/jdv.70149

76. Plachouri K-M Florou V Georgiou V Georgiou S Cutaneous side effects of modern targeted therapy and immunotherapy in patients with dermatological malignancies Cancers (Basel) 2023 15 12 3126 10.3390/cancers15123126 37370736 PMC10296313 Plachouri K-M, Florou V, Georgiou V, Georgiou S. Cutaneous side effects of modern targeted therapy and immunotherapy in patients with dermatological malignancies. Cancers (Basel). 2023;15(12):3126. 37370736 10.3390/cancers15123126 PMC10296313

77. Gisondi P Geat D Mattiucci A Lombardo F Santo A Girolomoni G Incidence of adverse cutaneous reactions to epidermal growth factor receptor inhibitors in patients with non-small-cell lung cancer Dermatology 2021 237 6 929 933 10.1159/000513233 33508823 Gisondi P, Geat D, Mattiucci A, Lombardo F, Santo A, Girolomoni G. Incidence of adverse cutaneous reactions to epidermal growth factor receptor inhibitors in patients with non-small-cell lung cancer. Dermatology. 2021;237(6):929–33. 10.1159/000513233. 33508823 10.1159/000513233

78. Apalla Z Freites-Martinez A Grafanaki K Management of human epidermal growth factor receptor inhibitors-related acneiform rash: a position paper based on the first Europe/ USA Delphi consensus process J Eur Acad Dermatol Venereol 2025 39 4 730 741 10.1111/jdv.20391 39460590 PMC11934016 Apalla Z, Freites-Martinez A, Grafanaki K, et al. Management of human epidermal growth factor receptor inhibitors-related acneiform rash: a position paper based on the first Europe/ USA Delphi consensus process. J Eur Acad Dermatol Venereol. 2025;39(4):730–41. 10.1111/jdv.20391. 39460590 10.1111/jdv.20391 PMC11934016

79. Lee JH Ju HJ Kwon HS Efficacy of topical epidermal growth factor cream for patients with epidermal growth factor receptor inhibitor-induced acneiform eruption: a randomized controlled trial Br Dermatol 2019 10.1111/bjd.18340 31301244 Lee JH, Ju HJ, Kwon HS, et al. Efficacy of topical epidermal growth factor cream for patients with epidermal growth factor receptor inhibitor-induced acneiform eruption: a randomized controlled trial. Br Dermatol. 2019. 10.1111/bjd.18340. 10.1111/bjd.18340 31301244

80. Bang AS Fay CJ LeBoeuf NR Multi-center retrospective review of vitiligo-like lesions in breast cancer patients treated with cyclin-dependent kinase 4 and 6 inhibitors Breast Cancer Res Treat 2024 204 3 643 647 10.1007/s10549-023-07217-2 38224427 Bang AS, Fay CJ, LeBoeuf NR, et al. Multi-center retrospective review of vitiligo-like lesions in breast cancer patients treated with cyclin-dependent kinase 4 and 6 inhibitors. Breast Cancer Res Treat. 2024;204(3):643–7. 10.1007/s10549-023-07217-2. 38224427 10.1007/s10549-023-07217-2

81. Shi VJ Rodic N Gettinger S Clinical and histologic features of lichenoid mucocutaneous eruptions due to anti-programmed cell death 1 and anti-programmed cell death ligand 1 immunotherapy JAMA Dermatol 2016 152 10 1128 10.1001/jamadermatol.2016.2226 27411054 PMC6108080 Shi VJ, Rodic N, Gettinger S, et al. Clinical and histologic features of lichenoid mucocutaneous eruptions due to anti-programmed cell death 1 and anti-programmed cell death ligand 1 immunotherapy. JAMA Dermatol. 2016;152(10):1128. 10.1001/jamadermatol.2016.2226. 27411054 10.1001/jamadermatol.2016.2226 PMC6108080

82. Ren Z Zhu K Kang H Randomized controlled trial of the prophylactic effect of urea-based cream on sorafenib-associated hand–foot skin reactions in patients with advanced hepatocellular carcinoma J Clin Oncol 2015 33 8 894 900 10.1200/JCO.2013.52.9651 25667293 Ren Z, Zhu K, Kang H, et al. Randomized controlled trial of the prophylactic effect of urea-based cream on sorafenib-associated hand–foot skin reactions in patients with advanced hepatocellular carcinoma. J Clin Oncol. 2015;33(8):894–900. 10.1200/JCO.2013.52.9651. 25667293 10.1200/JCO.2013.52.9651

83. Chanprapaph K Rutnin S Vachiramon V Multikinase inhibitor-induced hand–foot skin reaction: a review of clinical presentation, pathogenesis, and management Am J Clin Dermatol 2016 17 4 387 402 10.1007/s40257-016-0197-1 27221667 Chanprapaph K, Rutnin S, Vachiramon V. Multikinase inhibitor-induced hand–foot skin reaction: a review of clinical presentation, pathogenesis, and management. Am J Clin Dermatol. 2016;17(4):387–402. 10.1007/s40257-016-0197-1. 27221667 10.1007/s40257-016-0197-1

84. Minta A Rose L Park C Retrospective cohort study of CDK4/6-inhibitor-induced alopecia in breast cancer patients Support Care Cancer 2023 31 12 717 10.1007/s00520-023-08160-0 37991653 Minta A, Rose L, Park C, et al. Retrospective cohort study of CDK4/6-inhibitor-induced alopecia in breast cancer patients. Support Care Cancer. 2023;31(12):717. 10.1007/s00520-023-08160-0. 37991653 10.1007/s00520-023-08160-0

85. Nazzaro G Giacalone S Bortoluzzi P Veraldi S Marzano AV Erosive pustular dermatosis of the scalp induced by gefitinib: case and review of the literature Dermatol Online J 2021 10.5070/D3272052385 33818981 Nazzaro G, Giacalone S, Bortoluzzi P, Veraldi S, Marzano AV. Erosive pustular dermatosis of the scalp induced by gefitinib: case and review of the literature. Dermatol Online J. 2021. 10.5070/D3272052385. 33818981

86. Starace M Alessandrini A Baraldi C Piraccini BM Erosive pustular dermatosis of the scalp: challenges and solutions Clin Cosmet Investig Dermatol 2019 12 691 698 10.2147/CCID.S223317 31571969 PMC6747878 Starace M, Alessandrini A, Baraldi C, Piraccini BM. Erosive pustular dermatosis of the scalp: challenges and solutions. Clin Cosmet Investig Dermatol. 2019;12:691–8. 10.2147/CCID.S223317. 31571969 10.2147/CCID.S223317 PMC6747878

87. Junejo MH Kentley J Rajpopat M Tan XL Mohd Mustapa MF Harwood CA Therapeutic options for erosive pustular dermatosis of the scalp: a systematic review Br J Dermatol 2021 184 1 25 33 10.1111/bjd.19026 32163590 Junejo MH, Kentley J, Rajpopat M, Tan XL, Mohd Mustapa MF, Harwood CA. Therapeutic options for erosive pustular dermatosis of the scalp: a systematic review. Br J Dermatol. 2021;184(1):25–33. 10.1111/bjd.19026. 32163590 10.1111/bjd.19026

88. Wang C-W Yang LY Chen CB Randomized, controlled trial of TNF-α antagonist in CTL-mediated severe cutaneous adverse reactions J Clin Invest 2018 128 3 985 996 10.1172/JCI93349 29400697 PMC5824923 Wang CW, Yang LY, Chen CB, et al. Randomized, controlled trial of TNF-α antagonist in CTL-mediated severe cutaneous adverse reactions. J Clin Invest. 2018;128(3):985–96. 10.1172/JCI93349. 29400697 10.1172/JCI93349 PMC5824923

89. Zhang M Fu Y Song Y Gao X Wang J Zhang B Immune-related toxic epidermal necrolysis affecting trachea mucosal epithelium: a case report and literature review Front Pharmacol 2024 10.3389/fphar.2024.1454015 39494351 PMC11527638 Zhang M, Fu Y, Song Y, Gao X, Wang J, Zhang B. Immune-related toxic epidermal necrolysis affecting trachea mucosal epithelium: a case report and literature review. Front Pharmacol. 2024. 10.3389/fphar.2024.1454015. 39494351 10.3389/fphar.2024.1454015 PMC11527638

90. Ciardiello T Pinto D Marotta L Giuliani G Rinaldi F Effects of fermented oils on alpha-biodiversity and relative abundance of cheek resident skin microbiota Cosmetics 2020 7 2 34 10.3390/cosmetics7020034 Ciardiello T, Pinto D, Marotta L, Giuliani G, Rinaldi F. Effects of fermented oils on alpha-biodiversity and relative abundance of cheek resident skin microbiota. Cosmetics. 2020;7(2):34. 10.3390/cosmetics7020034.

91. Egert M Simmering R Riedel C The association of the skin microbiota with health, immunity, and disease Clin Pharmacol Ther 2017 102 1 62 69 10.1002/cpt.698 28380682 Egert M, Simmering R, Riedel C. The association of the skin microbiota with health, immunity, and disease. Clin Pharmacol Ther. 2017;102(1):62–9. 10.1002/cpt.698. 28380682 10.1002/cpt.698

92. Majchrzak W Motyl I Śmigielski K Biological and cosmetical importance of fermented raw materials: an overview Molecules 2022 27 15 4845 10.3390/molecules27154845 35956792 PMC9369470 Majchrzak W, Motyl I, Śmigielski K. Biological and cosmetical importance of fermented raw materials: an overview. Molecules. 2022;27(15):4845. 10.3390/molecules27154845. 35956792 10.3390/molecules27154845 PMC9369470

93. Kim JH Kim J-E Kang S-J Yoon J-K Exosomes and exosome-mimetics for atopic dermatitis therapy Tissue Eng Regen Med 2025 22 4 381 396 10.1007/s13770-024-00695-5 39832066 PMC12122991 Kim JH, Kim J-E, Kang S-J, Yoon J-K. Exosomes and exosome-mimetics for atopic dermatitis therapy. Tissue Eng Regen Med. 2025;22(4):381–96. 10.1007/s13770-024-00695-5. 39832066 10.1007/s13770-024-00695-5 PMC12122991

94. Li J Wang J Chen Z Emerging role of exosomes in cancer therapy: progress and challenges Mol Cancer 2025 24 1 13 10.1186/s12943-024-02215-4 39806451 PMC11727182 Li J, Wang J, Chen Z. Emerging role of exosomes in cancer therapy: progress and challenges. Mol Cancer. 2025;24(1):13. 10.1186/s12943-024-02215-4. 39806451 10.1186/s12943-024-02215-4 PMC11727182

95. Zhu Y Yang H Xue Z Tang H Chen X Liao Y Mesenchymal stem cells-derived small extracellular vesicles and apoptotic extracellular vesicles for wound healing and skin regeneration: a systematic review and meta-analysis of preclinical studies J Transl Med 2025 23 1 364 10.1186/s12967-024-05744-0 40128791 PMC11934660 Zhu Y, Yang H, Xue Z, Tang H, Chen X, Liao Y. Mesenchymal stem cells-derived small extracellular vesicles and apoptotic extracellular vesicles for wound healing and skin regeneration: a systematic review and meta-analysis of preclinical studies. J Transl Med. 2025;23(1):364. 10.1186/s12967-024-05744-0. 40128791 10.1186/s12967-024-05744-0 PMC11934660