Diagnosis and treatment of cutaneous adverse effects of targeted therapy, antibody–drug conjugates, and immunotherapy in cancer patients: a national consensus statement by the Spanish Society of Medical Oncology and the Spanish Academy of Dermatology and Venereology

Diagnosis and treatment of cutaneous adverse effects of targeted therapy, antibody–drug conjugates, and immunotherapy in cancer patients: a national consensus statement by the Spanish Society of Medical Oncology and the Spanish Academy of Dermatology and Venereology | Clinical and Translational Oncology | Springer Nature Link Skip to main content Advertisement Log in Menu Find a journal Publish with us Track your research Search Saved research Cart Home Clinical and Translational Oncology Article Diagnosis and treatment of cutaneous adverse effects of targeted therapy, antibody–drug conjugates, and immunotherapy in cancer patients: a national consensus statement by the Spanish Society of Medical Oncology and the Spanish Academy of Dermatology and Venereology Special Article Open access Published: 28 January 2026 Volume 28 , pages 2603–2624 ( 2026 ) Cite this article You have full access to this open access article Download PDF Save article View saved research Clinical and Translational Oncology Aims and scope Submit manuscript Diagnosis and treatment of cutaneous adverse effects of targeted therapy, antibody–drug conjugates, and immunotherapy in cancer patients: a national consensus statement by the Spanish Society of Medical Oncology and the Spanish Academy of Dermatology and Venereology Download PDF Margarita Majem ORCID: orcid.org/0000-0002-9919-7485 1 , Kevin Molina Mata 2 na1 , Ander Mayor Ibarguren 3 na1 , Marta Zafra Poves 4 na1 , Celia Requena 5 na1 , Francisco de Asis Aparisi Aparisi ORCID: orcid.org/0000-0002-1468-1375 6 na1 , Cristina Carrera ORCID: orcid.org/0000-0003-1608-8820 7 , 8 na1 , Ana Blasco Cordellat ORCID: orcid.org/0000-0001-5889-0382 9 na1 , Azael Freites-Martinez ORCID: orcid.org/0000-0002-3121-5667 10 na1 & … Onofre Sanmartin 5 Show authors 6120 Accesses 5 Citations 5 Altmetric Explore all metrics Abstract Cancer remains a leading cause of mortality in developed countries, with advancements in targeted therapies, antibody–drug conjugates (ADCs), and immunotherapy significantly improving patient survival. However, these treatments often result in cutaneous adverse effects (AEs), impacting the skin, mucosa, hair, and nails. This expert consensus statement provides a comprehensive overview of the mechanisms behind these skin toxicities, their clinical manifestations, and the importance of rapid diagnosis and treatment. The spectrum of skin toxicities ranges from mild reactions such as xerosis and pruritus to severe, potentially life-threatening conditions such as Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). This statement underlines the need for healthcare professionals to work in multidisciplinary teams, use standardized classification systems such as the Common Terminology Criteria for AEs (CTCAE) v5.0, educate patients on preventive measures, and establish clinical management guidelines to mitigate these AEs. By understanding the pathophysiological mechanisms and implementing effective management strategies such as photoprotection, gentle hygiene, emollients, prophylactic antibiotics, or specific hair and nail care, the quality of life for cancer patients can be significantly improved, ensuring continuity of oncologic treatment and improving overall survival. Similar content being viewed by others Dermatologic Adverse Events Chapter © 2018 Cutaneous Adverse Events of Systemic Melanoma Treatments Chapter © 2019 Cutaneous Adverse Events of Systemic Melanoma Treatments Chapter © 2019 Explore related subjects Discover the latest articles, books and news in related subjects, suggested using machine learning. Special Dermatology Targeted therapies Skin cancer Dermatological Therapy Dermatology Cancer Immunotherapy Inflammatory Skin Diseases and Patient Quality of Life Introduction Cancer is the second leading cause of mortality in developed countries, with a progressive increase in survival secondary to the implementation of new therapies [ 1 ]. However, the adverse effects (AEs) of cancer therapies are multiple, and the skin and its appendages are among the main organs affected, with alterations in up to 50% of patients receiving immunotherapy [ 2 ] or in up to 72% of those receiving chemotherapy [ 3 ]. In recent decades, multiple advances have been made in the understanding of oncogenic mechanisms. Numerous antineoplastic therapies have been developed, allowing better disease control and survival by targeting specific tumorigenic molecular mechanisms. The most common therapies include immunotherapy, antibody–drug conjugate (ADCs), and targeted therapies. Unfortunately, these therapies can cause AEs, including skin toxicity, affecting the skin, mucosa, scalp, and/or nails. Acneiform eruptions, hand‒foot reactions, alopecia, and eczema-like exanthema are frequent clinical manifestations [ 4 ]. The spectrum of skin toxicities is extremely varied: AEs usually present as mild skin reactions (xerosis, pruritus, urticaria and/or macular rash), although occasionally, toxicity evolves into serious, potentially lethal forms. While around 30% skin toxicity is caused by immunotherapy [ 5 , 6 , 7 ], approximately 20–60% is caused by ADCs [ 8 ], and 25–85% is caused by treatment with epidermal growth factor receptor (EGFR) and MAP-kinase inhibitors [ 9 ]. The mechanisms behind skin toxicity vary depending on the different mechanisms of action of each therapy. AEs caused by targeted therapies are denominated “on-target” damage. An example is the case of anti-EGFR therapies, which can produce papulopustular eruptions due to damage to basement membrane cells. Immunotherapy causes a multitude of immune-related phenomena, such as lichenoid reactions or vitiligo, as well as reactivation of pre-existing skin conditions (e.g., psoriasis). Skin toxicity must be diagnosed and treated rapidly, as it can highly impact patients’ quality of life [ 10 ], causing delays, dose reductions, and even the definitive suspension of antineoplastic treatment, which can affect survival [ 11 ]. Interruptions and discontinuations of anti-EGFR treatment due to acneiform reactions have been reported in up to 76% and 32% of patients, respectively [ 12 ]. Owing to the high frequency of cutaneous AEs, it is essential for healthcare professionals to work in multidisciplinary teams, carry out preventive health education for patients, and establish clinical management guidelines. Classification of targeted therapies, ADCS, and immunotherapies and description of the mechanism of action by which they trigger skin toxicity Among specific toxicities directly associated with drug mechanisms of action, cutaneous toxicity is highly relevant because it reflects interactions between skin biology, the immune system, and drug mechanisms of action [ 13 , 14 ]. The main pathophysiological mechanisms involved are described below according to the type of treatment (Table 1 ): Table 1 Mechanisms of skin toxicity according to type of cancer treatment Full size table Targeted therapies These agents act on specific molecular targets involved in tumor proliferation. Tyrosine kinase inhibitors (TKIs) act on kinases involved in cell signaling. EGFR TKIs are expressed in keratinocytes, hair follicles, and sebaceous glands, so their inhibition results in disruption of the skin barrier, abnormal keratinization, and follicular inflammation mediated by IL-8, which generates acneiform rash and paronychia [ 15 , 16 ]. Antiangiogenic TKIs induce microvascular damage and dermal stress, with the activation of cytotoxic pathways in keratinocytes and the appearance of acral lesions, erythrodysesthesia or pigmentary alterations [ 9 , 16 ]. TKIs act via MAPKs (e.g., BRAF inhibitors) through paradoxical activation in healthy cells and induce proliferative skin lesions, and their combination with antiMEKs has been shown to reduce the incidence of these toxicities [ 17 ]. CDK4/6 inhibitors act by blocking the progression of the cell cycle from G1 to S, reducing epidermal renewal, and can modulate the activity of skin immune cells, favoring a proinflammatory environment [ 18 ]. Antibodies targeting molecular alterations Pure monoclonal antibodies: Anti-HER2 antibodies (trastuzumab, pertuzumab) have a low incidence of skin toxicity since HER2 is not significantly expressed in the skin. However, in combination with TKIs, they can amplify EGFR inhibition and increase the risk of skin rash [ 19 , 20 ]. Anti-VEGF agents (bevacizumab) induce rare events, such as ulceration or delayed healing, by interfering with dermal angiogenesis [ 21 ]. Bispecific antibodies: These antibodies simultaneously recognize two different antigens, allowing more specific and powerful mechanisms of action. Amivantamab [ 22 ], which is directed against EGFR and MET, has high skin toxicity (up to 78%), mainly due to its ability to inhibit EGFR by altering keratinocyte function and triggering IL-8-mediated follicular inflammation. Paronychia is associated with epidermal disruption and microtrauma. The role of MET in this toxicity is not clearly defined. Antibody–drug conjugates (ADCs) These drugs combine high specificity and targeted cytotoxicity. Their toxicity is attributed to the premature systemic release of the cytotoxic drug into the bloodstream, which can affect keratinocytes and epidermal structures. Furthermore, the basal expression of the target antigen in the skin (e.g., Nectin-4, Trop-2) allows ADCs to bind to non-tumor cells. Immune-mediated dermal inflammation has also been described [ 23 ]. They can cause dermatological manifestations of variable intensity which can be potentially life-threatening. Immunotherapy Immune checkpoint inhibitors (anti-PD-(L)1 and anti-CTLA-4) induce skin toxicity via the dysregulation of immune tolerance. The polyclonal activation of T lymphocytes against self-antigens, the increase in proinflammatory cytokines (IL-6, IFN-γ), and Tregs reduction explain the appearance of rash, eczema, lichen planus or vitiligo [ 24 ]. These reactions are more frequent and intense with ipilimumab (anti-CTLA-4) because of its greater impact on Tregs [ 2 ]. Types of cutaneous AEs Papulopustular eruption and skin xerosis caused by targeted therapies Papulopustular eruption Papulopustular eruption (PPE), also called acneiform eruption, is the most frequent form of skin toxicity induced by anti-EGFR therapies, both monoclonal antibodies (mAbs) and TKIs. This rash has also been occasionally described with the use of mTOR inhibitors and BRAF inhibitors [ 9 ]. Table 2 summarizes the anti-EGFR agents currently available in Spain, together with the incidence of PPE described in pivotal or safety trials of the different agents [ 22 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. As shown in the table, in general, the presence of PPE is more frequent and more intense with mAbs than with TKIs. Table 2 Incidence of papulopustular eruption described with different anti-EFGR agents Full size table EGFR is highly expressed in basal keratinocytes and in adnexal structures of normal skin. Its inhibition interferes with the proliferation, differentiation, and repair of the follicular epithelium, leading to perifollicular neutrophilic inflammation that simulates sterile folliculitis [ 9 ]. On the other hand, it considerably reduces the presence of epidermal antimicrobial peptides, which facilitates frequent superinfection with Staphylococcus aureus [ 34 ]. Clinically, PPE consists of erythematous papules and sterile pustules without comedones located in seborrheic areas such as the face, scalp, and upper trunk (Fig. 1 ). It appears during the first to second weeks of treatment and reaches maximum intensity during the third and fourth weeks. It is more frequent and more intense in patients with light phototypes, worsening with sun exposure. Over time, the lesions tend to remit, being replaced by xerosis, desquamation, or even eczematous lesions [ 20 ]). Fig. 1 Full size image CTCAE v5.0 classification of severity of papulopustular eruption Importantly, in up to 40% of patients, more severe lesions may develop, with erosions, scabs, intense itching, pain and bacterial infection, especially by Staphylococcus aureus [ 15 , 35 ]. In fact, in a significant percentage of patients, the clinical course of PPE changes after 3 months, with the appearance of pustular and crusty lesions in more peripheral regions than those described for PPE, coinciding with bacterial infection, especially in hairy areas (Fig. 2 ). Fig. 2 Full size image Patient presenting with papular-pustular eruption and Staphylococcus aureus superinfection, with suppurative lesions, meliceric scabs and extension of the lesions to the upper extremities and scalp The classification of the severity of PPE proposed by the Common Terminology Criteria for AEs (CTCAE) v5.0 is illustrated in Fig. 1 [ 36 ] and is useful when making therapeutic decisions. Notably, the intensity of PPE is associated with response to treatment [ 37 ]. Implementing effective prophylaxis reduces the incidence and severity of PPE, along with unnecessary dose adjustments or treatment suspensions [ 38 ]. Patients should use emollients that restore the skin barrier (with urea or ceramides), apply photoprotection with a sun protection factor (SPF) greater than 30, and avoid harsh soaps. Preventive treatment with tetracyclines is especially useful during the first 6‒8 weeks of treatment. The use of doxycycline at doses of 100 mg every 12 h or minocycline at doses of 100 mg per day orally has resulted in a significant reduction in the appearance of PPE, especially its severe forms [ 39 ]. Similarly, the topical use of low-potency corticosteroids and clindamycin has been recommended in empirical and consensus studies to avoid infections and itching associated with rash [ 40 ]. Treatment of PPE should be prescribed depending on severity according to CTCAE criteria, as summarized in Table 3 . The treatment includes the use of oral tetracyclines if they have not been used previously, dose adjustments or suspension of anti-EGFR treatment, obtaining bacterial cultures of the lesions when infection by Staphylococcus aureus is suspected, and control of pruritus and pustular lesions with topical corticosteroids or clindamycin [ 41 ]. Table 3 Treatment of papulopustular eruption caused by anti-EGFR drugs Full size table Cutaneous xerosis Xerosis is a common form of skin toxicity induced by various targeted therapies, including anti-EGFR agents, BRAF inhibitors, and MEK inhibitors. Cutaneous xerosis affects more than 15% of patients receiving targeted treatment [ 42 ]. EGFR inhibition interferes with keratinocyte maturation and intercellular lipid synthesis, altering skin barrier function and facilitating transepidermal water loss [ 20 ]. Cutaneous xerosis presents as intense dryness, peeling, fissures, itching, and even secondary eczematization. Clinically, xerosis appears sequentially after PPE. Eczema secondary to xerosis is called “craquelé” or asteatotic eczema (Fig. 3 ). It presents as dermatitis on very dry skin, with superficial cracks reminiscent of a “dry riverbed” or “cracked porcelain”, generally associated with intense itching. The most affected areas are usually the extremities, palms, soles, and areas exposed to the elements. Fig. 3 Full size image Patient with cracked eczema on the lower limbs secondary to cutaneous xerosis caused by anti-EGFR therapy The severity of cutaneous xerosis graded by CTCAE v5.0 classifies xerosis as Grade 1 (mild dryness or no symptoms), Grade 2 (mild itching or fissures), Grade 3 (eczema, pain and functional impairment), and Grade 4 (extensive infection and the need for hospitalization). In general, to prevent cutaneous xerosis induced by targeted therapies, emollients with urea (5–10%), lactic acid or ceramides should be used from the start of treatment. It is crucial to avoid harsh soaps, prolonged baths, and exposure to extreme temperatures. When secondary eczematization or bacterial infection occurs, topical corticosteroids of moderate potency associated with topical or oral antibiotics are indicated [ 42 ]. Hand–foot skin reaction caused by multi-kinase inhibitors TKIs have been associated with various cutaneous AEs, including nonspecific morbilliform rash, mucositis, alopecia, changes in skin color, splinter hemorrhages, edema, ulcers and delayed healing, palmar-plantar rash, and scrotal or vulvar erythema-eczema. Hand–foot skin reaction is a very characteristic type of toxicity caused by multi-kinase inhibitors [ 43 , 44 , 45 , 46 , 47 , 48 ] differing from the palmar-plantar syndrome induced by classical chemotherapy (Table 4 ). It develops between 1 and 6 weeks after the start of treatment, is dose-dependent and is usually preceded by paresthesia or pain. Hand–foot skin reaction is characterized by the appearance of intensely painful, erythematous lesions on the palms and soles (Fig. 4 a). Later, the lesions become inflammatory and sometimes yellowish or pseudobullous (Fig. 4 b), with an easily recognizable appearance that is halfway between a “callus” (or heloma) and a blister. Lesions can also appear on the lateral surfaces of the fingers or periungual region and are usually worsened by heat and friction. In the most severe forms, areas of thickened skin appear, which, in addition to being painful, hinder the mobility and functionality of the hands and feet (Fig. 4 c). Scrotal or vulvar erythema and erosion, which have been described with sorafenib, pazopanib, and cabozantinib, among others, also develop in some patients and are accompanied by intense pain, which may be dose limiting (Fig. 4 d). Table 4 Differences between hand–foot syndrome caused by conventional chemotherapy and hand–foot skin reaction caused by multi-kinase inhibitors Full size table Fig. 4 Full size image a Erythematous lesion on the weight-bearing surface of the first toe (Grade 1 toxicity). b Hyperkeratosic and pseudoampollar yellowish lesions on weight-bearing points of soles (Grade 2 toxicity). c Marked hyperkeratosis with intensely painful fissures on the palms of the hands (Grade 3 toxicity). d Scrotal involvement with intensely painful erythematous and desquamative lesions in the same patient from c Although hand‒foot syndrome does not directly affect survival, it can have a considerable effect on quality of life and often requires dose reduction or even stopping therapy. This clinical presentation is most common with VEGFR inhibitors, occurring in 60% of regorafenib patients, 35.5% of patients in treatment with cabozantinib, and 27% of patients with lenvatinib, and is also frequently observed with sunitinib, sorafenib, and pazopanib. Preventive strategies include eliminating helomas and areas of hyperkeratosis before starting treatment, as well as the use of pressure-relief insoles. Hot water and tight shoes should be avoided during treatment, and the use of cotton socks is recommended to minimize friction. Oral zinc supplements have also been shown to be useful [ 49 ], as have antiperspirants [ 50 ]. For Grade 1 lesions, emollient and keratolytic creams (urea, 20–40%, or salicylic acid, 6%) should be prescribed. For Grade 2 lesions, clobetasol ointment, 0.05%, should be added. In addition, lidocaine cream, 2%, and oral pain relievers help control pain in patients with mucositis. In very painful cases, it may be necessary to reduce the dose to reduce the severity to Grade 0–1. In Grade 3 injuries, in addition to the previous recommendations, treatment should be paused. If reintroduced, it should be started at half the original dose. For the treatment of residual hyperkeratotic lesions, the use of urea cream, 40 tazarotene cream, 0.1%, or fluorouracil cream, 5%, is recommended. Hair follicle alterations Hair follicle alterations produced by various targeted therapies can be classified into the following main categories (Table 5 ): Table 5 Main hair disorders associated with targeted cancer therapy a Full size table Alterations in quantity of hair follicles Alopecia Alopecia can be produced by almost any type of targeted cancer therapy, including inhibitors of EGFR, HER-2, BRAF, MEK, the KIT/BCR-ABL fusion gene, VEGF/VEGFR, Hedgehog, the proteasome, PI3K, ALK, HDAC, RANKL, and PARP. In addition, anti-CD30 (brentuximab), anti-CD52 (alemtuzumab), anti-PD-1/PD-L1, and anti-CTLA-4 immunotherapies may also produce alopecia [ 51 ]. Incidence of treatment-related alopecia is variable and is highest for Hedgehog inhibitors, representing one of the most frequent AEs associated with these therapies. In most cases, alopecia is diffuse and mimics slow-onset androgenic alopecia, unlike the alopecia observed with the anagen effluvium of classical chemotherapy. The mechanisms responsible for alopecia induced by targeted therapies vary according to the pharmacological group and include blockade of trophic signals (EGFR inhibitors) (Fig. 5 a), inhibition of the anagen cycle (Hedgehog), and follicular microischemia (VEGFR inhibitors) [ 52 ]. In contrast, alemtuzumab and immunotherapy can produce cases of plaque and universalis alopecia areata (non-scarring, immune-mediated inflammatory alopecia) [ 52 ]. Fig. 5 Full size image a Anti-EFGR-induced hair loss secondary to trophic signal inhibition. b Trichomegaly caused by anti-EGFR therapy Regarding treatment and prevention of alopecia caused by targeted therapies, topical (2–5%) and/or low dose oral minoxidil can slow down alopecia and improve hair density [ 52 ]. Intralesional PRP may also be helpful, although evidence is limited and should be used with precaution in patients with cancer [ 53 ]. In the case of alopecia areata, immunosuppressive therapies (such as intralesional or high-potency topical corticosteroids) should be added; the use of classical (methotrexate) or novel (JAK inhibitors) systemic therapies is more complex in the case of cancer patients and is generally not recommended [ 54 ]. Trichomegaly Trichomegaly is a frequent and characteristic effect of EGFR inhibitors and is believed to be caused by a prolonged anagen phase due to EGFR inhibition or immune modulation (Fig. 5 b) [ 55 ]. Eyelashes should be trimmed carefully. Electrolysis should be prescribed in the case of trichiasis. Facial hypertrichosis has also been described with anti-PD-1, EGFR, and PI3K inhibitors. Hair pigmentation alterations Hair hypochromia has been described as an AE of c-KIT/BCR-ABL inhibitors (imatinib, dasatinib) and VEGFR inhibitors (sunitinib, pazopanib). Hypochromia is more characteristic of c-KIT/BCR-ABL inhibition due to the KIT function in melanocytes. Paradoxical repigmentation of graying hair has been associated with anti-PD-1/PD-L1, probably through re-immune stimulation of melanocytes [ 56 ]. The therapeutic approach toward therapy-induced pigment alterations includes patient information and cosmetic treatment; hypochromia usually reverts when therapy is withdrawn or spaced. Alterations in hair consistency Frizz is a characteristic effect of EGFR inhibitors. Curling is also seen with BRAF and MEK inhibitors, as well as frailty with many targeted therapies [ 57 ]. Trichorrhexis nodosa has been reported with trametinib. To prevent treatment-related frizz, curling, or frailty, patients should avoid heat and harsh hair-styling techniques, and the use of silicone conditioners is recommended. When treatment-related alterations in hair consistency appear, regular hair cutting and the use of repairing oils is recommended. Inflammatory alopecia Less frequently, pustular folliculitis may occur, evolving into crusts adhering to the base of various follicles and leading to ulcers, which mimic cases of folliculitis decalvans or erosive pustular dermatosis of the scalp [ 58 ]. Pustular folliculitis has been described in association with EGFR inhibitors, as well as bispecific antibodies such as amivantamab [ 59 ]. It causes significant pain, and Staphylococcus aureus infection is common, perpetuating the inflammatory stimulus after rupture of the infundibulum due to EGFR blockage. Preventive treatment consists of the use of doxycycline 100 mg/12 h and topical clindamycin from the first week of treatment [ 60 ]. Treatment consists of antibiotics with anti-staphylococcal activity, oral prednisone, and high-potency topical corticosteroids. In selected cases, isotretinoin can be administered at a dose of 0.5 mg/kg. A good response to oral dapsone has also been reported in the case of amivantamab. In severe cases, it may be necessary to temporarily interrupt and/or reduce the dose of the causative agent to avoid permanent scarring. Nail alterations Most targeted cancer therapies can induce nail alterations that significantly affect patients’ quality of life. They usually appear between 4 and 8 weeks of treatment and, in some cases, are associated with a better antitumor response [ 10 , 61 ]. EGFR inhibitors, as well as FGFR [ 62 ], MEK, mTOR, CDK4/6, and multi-kinase inhibitors, mainly affect periungual structures. Paronychia is the most frequent alteration, with an estimated incidence of 17–40%, especially in the case of monoclonal antibodies (Fig. 6 a, b) and bispecific antibodies such as amivantamab [ 22 ]. Reactive endothelial capillary proliferations such as periungual pyogenic granulomas and deep and painful fissures may appear and are associated with xerosis and skin fragility. In addition, the possibility of bacterial superinfection in already altered base areas is notable. The mechanism by which anti-EGFR drugs induce periungual inflammation is similar to that of the papulopustular reaction, which is related to epidermal atrophy of the periungual tissue. Fig. 6 Full size image a Paronychia and finger onycholysis due to panitumumab. b Paronychia and early pyogenic granuloma caused by cetuximab. c Pembrolizumab-induced extensive psoriasis, with onycholysis and subungual hyperkeratosis of all nails, associated with extensive and generalized erythematous plaques Immunotherapy can both induce and aggravate dermatoses that affect the nail apparatus, such as psoriasis or lichen planus, causing pitting, onycholysis, subungual hyperkeratosis (Fig. 6 c), or the typical onychorrhexis of lichen planus. The most frequent alterations of the nail plate include onycholysis, mainly caused by tyrosine kinase inhibitors of FGFR and mTOR and photo-onycholysis, caused by photosensitizing drugs such as vemurafenib. Onychoschizia (brittle nails), splinter hemorrhages (mainly caused by VEGF inhibitors), and pigmentary changes such as melanonychia or leukonychia (caused by TKIs or c-KIT inhibitors) are other frequent alterations. Prevention includes avoiding trauma and aggressive manipulation, wearing comfortable shoes and gloves, and daily use of emollients. There is limited evidence for the use of oral biotin as prophylaxis for nail alterations. Treatment of nail alterations should be prescribed according to severity and should be reevaluated every 2 weeks [ 10 , 63 ]. Grade 1 toxicity (minimal periungual fold edema) may be treated with antiseptic solutions (iodine, chlorhexidine, hypochlorite, or acetic acid, 10–20%) and topical corticosteroids. The addition of culture-specific topical or oral antibiotics to powerful corticosteroids is recommended for patients with Grade 2 toxicity (marked edema, minimal exudation and onycholysis). For patients with intolerable Grade 3 or 2 nail alterations (marked exudation, onycholysis and impaired quality of life), c ancer treatment should be interrupted, systemic anti-inflammatories should be added, and nail avulsion should be considered. Finally, in the case of pyogenic pseudogranulomas, surgical excision, intralesional corticosteroids, propranolol cream, 1%, or occlusion with timolol gel, 0.5%, for 1 month is recommended [ 64 ]. Alterations of healing/ulcers by antiangiogenic medication and alterations of skin pigmentation by targeted treatments Healing disorders and ulcers from antiangiogenic drugs A common AE of all antiangiogenic drug is delay in healing and the formation of ulcers that are difficult to manage [ 65 ], mainly due to VEGF inhibition but also facilitated by the inhibition of fibroblast growth factor (FGF). This AE can be observed in various contexts, especially after surgical procedures, when suture dehiscence, hemorrhages, and delayed healing may occur (Fig. 7 a). Therefore, antiangiogenic drugs should be suspended a few weeks before surgery, depending on each specific drug’s half-life. In the case of bevacizumab, a minimum of 4 weeks is recommended, whereas for tyrosine kinase inhibitors, a week before surgery is sufficient because of their shorter half-life [ 65 ]. Antiangiogenic therapy should not be reintroduced until complete healing is achieved (between 2 and 4 weeks after surgery). Fig. 7 Full size image a Absence of healing 6 months after a 6 mm punch biopsy in a patient receiving pazopanib. b Refractory venous ulcer associated with cabozantinib. c Yellowish pigmentation on forearms caused by sunitinib. d Spotted pigmentation on forehead caused by vandetanib Antiangiogenic drugs also induce ulcers when used concomitantly or close to radiotherapy [ 66 , 67 ] or in the context of venous ulcers (Fig. 7 b). With lenvatinib, recalcitrant ulcers have also been described in the perineal area [ 68 , 69 ]. In situations of complex healing and/or chronic ulcers, temporary suspension of the drug may be indicated until healing is achieved. Most case reports of TKI-induced gangrenous pyoderma [ 70 ] correspond to this ulcer-promoting and healing-inhibiting effect of these drugs, rather than to true neutrophilic dermatoses. Alterations of skin pigmentation caused by targeted therapy Many targeted therapy drugs induce changes in the pigmentation of both the skin and its appendages, and some of these changes are drug-specific [ 71 , 72 ]. With c-KIT inhibitors, especially imatinib, localized or diffuse reversible cutaneous hypopigmentation and, more rarely, bluish pigmentation of the oral cavity are common. With sunitinib, the depigmentation of the hair with alternating depigmented bands corresponding to treatment cycle [ 73 ] is very characteristic. The yellowish pigmentation of the skin caused by sunitinib [ 74 ] is another characteristic alteration (Fig. 7 c). Both effects are reversible at the end of the treatment. Another type of relatively specific pigmentation is that induced by vandetanib (Fig. 7 d) in the form of irreversible bluish‒grayish pinpoint macules on the face and trunk [ 75 ]. Immunotherapeutic drugs can induce hyper and hypopigmentation, but more specifically, the induction of vitiligo has been described in these treatments and is especially common in patients with melanoma [ 5 , 76 ]. There are also cases of vitiligo caused by CDK4 inhibitors, especially ribociclib, which has also been associated with photosensitivity and reticulated hyperpigmentation. Although they are not exactly pigmentation alterations, it is interesting to remember that BRAF inhibitors, such as vemurafenib or dabrafenib, induce changes in previous melanocytic nevi or the appearance of new melanocytic nevi, sometimes eruptively [ 77 ]. Drug-induced photosensitivity Photosensitivity is an increasingly recognized dermatologic AE. Among targeted therapies, agents such as vemurafenib (BRAF inhibitor) and or vandetanib (multi-kinase RET inhibitor) are well-established causes of UVA-mediated phototoxicity, being reported in 35%–63% of patients [ 78 , 79 ], often presenting as painful erythema or blistering on sun-exposed areas. Newer agents including brigatinib [ 79 ], rucaparib [ 80 ], and ulixertinib [ 81 ] have also been linked to emerging patterns of photosensitivity. ICIs such as nivolumab and pembrolizumab have been associated with vitiligo-like depigmentation, particularly in melanoma patients. These pigmentary changes predominantly affect sun-exposed areas, thereby enhancing photoreactivity. While the incidence of direct photosensitivity is lower (e.g., ~ 1.5% with nivolumab) [ 5 , 82 ], pigmentary alterations may contribute to an increased risk of sunburn. Although ADCs are not typically associated with photosensitivity, recent reports suggest otherwise [ 23 ]. In the LOTIS-2 trial of loncastuximab tesirine, rashes occurred in 30% of patients, frequently in sun-exposed areas [ 83 ]. Post-marketing data also described persistent telangiectasias in sun-exposed skin [ 84 ]. These findings suggest possible off-target cutaneous DNA damage and UV sensitivity [ 23 ]. Diagnosis relies on clinical correlation, phototesting, and exclusion of alternative causes. Management includes stringent UVA/UVB protection, topical corticosteroids, and patient education. Importantly, recognition of these dermatologic toxicities is vital to prevent treatment discontinuation. Multidisciplinary collaboration between oncologists and dermatologists remains crucial for optimal care [ 85 ]. Proliferative effects induced by target therapies and immunotherapy During treatment with multi-kinase inhibitors, especially selective BRAF inhibitors in monotherapy, proliferative epithelial and melanocytic lesions have been described. Initially, it was estimated that one-third of patients develop squamous cell carcinomas, many of the keratoacanthoma type, between 8 and 16 weeks of treatment. This effect is attributed to the paradoxical activation of the MAP-kinase pathway in keratinocytes with mutations induced by UV radiation, such as RAS, and therefore , the risk is greater in patients with greater photodamage [ 86 , 87 ]. The combination of BRAF and MEK significantly reduces the incidence of these proliferations to less than 2% of patients [ 88 ]. Immunotherapy has also been associated with multiple keratoacanthomas, but in the context of lichenoid dermatoses and previous marked sun damage [ 89 ]. It is debated whether these lesions represent true carcinomas or a hypertrophic lichen planus-like inflammatory response in the context of cancer. Changes in pre-existing nevi have been observed with numerous targeted therapies, especially with multi-kinase inhibitors [ 90 ], and specifically in up to 55% of patients treated with BRAF inhibitors as monotherapy [ 91 ]. These changes include growth, regression or the appearance of dermoscopic alterations similar to those of melanomas. In this context, the development of new primary melanomas on pre-existing nevi (1–2%), detected by clinical and microscopic changes at approximately 14 weeks, has also been described histopathologically [ 92 ]. The combined use of BRAF and MEK inhibitors avoids these modifications [ 88 ]. It is unknown whether these modifications are fully reversible if targeted therapy is discontinued. Immunotherapy can also induce regression of nevi, especially in the context of vitiligo and patients with advanced melanoma and may also lead to the development of Sutton-type nevi. Nirogacestat is a gamma secretase inhibitor that blocks the activation of the Notch receptor, which is approved for desmoid tumors and can also lead to the development of non-melanoma skin cancer [ 93 ]. Regarding prevention and treatment, photoprotection and dermatological monitoring are essential, especially in patients with photodamage, numerous nevi or a history of skin cancer. In patients with multiple carcinomas, oral acitretin may be indicated for chemoprevention. Treatment of field cancerization (using topical or photodynamic therapies) and surgery are options. Eruptive keratoacanthomas can be treated with intralesional therapies such as methotrexate or 5-fluorouracil. Skin lesions induced by immune checkpoint inhibitors Immunomodulatory therapies with immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, but their use is associated with the occurrence of immune-mediated AEs, with skin toxicity being the most frequent. It is estimated that between 30 and 50% of patients develop some type of dermatological AE, which makes the skin one of the most affected target organs during immunotherapy [ 5 ]. Ten dermatological clinicopathological entities associated with ICI treatment have been recognized, which are summarized in Table 6 . For each immune-mediated dermatological AE, a grading scheme of severity is proposed, which considers the extent and morphology of the rash, the associated symptoms and the functional impact of the clinical picture [ 94 ]. Treatment depends on the clinical entity and the CTCAE grade (Table 7 ). Table 6 Cutaneous adverse effects caused by immune checkpoint inhibitors (ICIs) Full size table Table 7 Therapeutic alternatives for the most common immune-mediated adverse effects caused by immune checkpoint inhibitors (ICIs) Full size table Immunotherapy-induced maculopapular rash The most common skin manifestation associated with ICIs is maculopapular rash, which is present in approximately 30–68% of patients, especially those receiving anti-CTLA-4 treatments [ 2 ]. Its onset is early, occurring between 3 and 6 weeks after treatment. It is a pruritic inflammatory eruption characterized by the presence of macules and erythematous, symmetrical, confluent papules located on the trunk, back, arms and legs (Fig. 8 ). Although it usually has an eczematous appearance, it is classified as a morbilliform exanthematous reaction induced by systemic immune activation. Fig. 8 Full size image Maculopapular eruption due to therapy with immune checkpoint inhibitors The severity of the eruption is classified according to the CTCAE v5.0 criteria. Grade 1 refers to mild affectation, with less than 10% of the body surface affected and minimal symptoms, such as mild itching, without interference with daily life. Grade 2 implies moderate affectation, between 10 and 30% of the body surface, with more intense itching and a possible impact on daily instrumental activities. In Grade 3, the rash is extensive (more than 30%) and/or highly symptomatic, interfering with the patient’s self-care [ 95 ]. Management includes emollients, oral antihistamines, and topical corticosteroids of medium to high potency. In cases of Grade 3 or higher disease, it is necessary to temporarily suspend immunological treatment and administer systemic corticosteroids such as prednisone at doses of 0.5–1 mg/kg/day [ 96 , 97 ]. Immunotherapy-induced pruritus Isolated pruritus, without visible skin lesions, affects up to 13–36% of patients and may precede other skin toxicities. It usually appears between weeks 3 and 12 of treatment with ICIs, becoming disabling in some cases. Its treatment includes intensive hydration, oral antihistamines, and, in refractory cases, the use of agents such as gabapentin, aprepitant or doxepin, in addition to low-potency topical corticosteroids or calcineurin inhibitors [ 98 ]. Immunotherapy-related eczema Eczematous dermatitis is also common, with a prevalence close to 35% within the spectrum of immune-related skin reactions, presenting as erythematous, scaly, and itchy plaques [ 94 ]. Patients should be treated with basic skin care (hydration, gentle hygiene), along with topical corticosteroids of variable potency. In extensive or symptomatic cases, treatment with oral corticosteroids may be needed [ 5 ]. Lichenoid eruptions Lichenoid eruptions, present in up to 20% of cases, are associated mainly to PD-1/PD-L1 inhibitors. They usually appear 6 to 12 weeks after the start of treatment and consist of flat, erythematous‒violaceous papules, similar to primary lichen planus, which are sometimes intensely itchy (Fig. 9 ). The lesions are distributed on the trunk and extremities, occasionally in photoexposed areas. They can affect the oral or genital mucosa [ 99 ]. Fig. 9 Full size image Lichenoid eruption due to immune checkpoint inhibitors CTCAE v5.0 does not specifically classify lichenoid eruptions as an isolated category. However, these lesions are usually classified under the general term “immune-mediated skin reaction” based on the affected body surface, the intensity of the itching, and the functional impact on daily life. Mild cases (Grades 1 and 2) do not require ICI discontinuation and are treated with potent topical corticosteroids and antihistamines. The most serious cases require the suspension of immunotherapy and the use of prednisone at a dosage of 0.5 mg/day for 3 weeks. Notably, the suspension of immunotherapy is not always accompanied by complete remission of lichenoid eruption. Corticosteroid-resistant patients require the use of immunosuppressants such as methotrexate or retinoids such as acitretin [ 100 ]. Psoriasis and psoriasiform eruptions De novo psoriasis or exacerbations of pre-existing psoriasis exacerbation occur in approximately 4% of patients. Clinical presentations, in order of frequency, include plaque, palmar-plantar, gouty and pustular psoriasis [ 100 ]. Management includes topical corticosteroids, calcipotriol, narrowband UVB phototherapy and, in severe cases, acitretin or methotrexate. If biological treatment is needed, anti-IL-17 or anti-IL-23 agents are recommended, avoiding anti-TNF agents because of their unfavorable safety profile in cancer patients [ 100 ]. Autoimmune bullous diseases Bullous pemphigoid has been described in up to 1% of patients treated with anti-PD-1/PD-L1 therapy. It usually starts late, from weeks 13–35 of treatment, even presenting after the end of treatment [ 101 ]. Clinically, it presents with intense itching accompanied by tense blisters, scabs, and erosions located on the trunk, folds, and extremities. Occasionally, it appears as pemphigoid located in the extremities and is associated with lichen planus pemphigoides. Treatment depends on the severity and extent of the rash. In mild and localized forms, high-potency topical corticosteroids are used; in severe forms, systemic corticosteroids are administered, and a suspension of the ICI is considered, although it does not always induce remission of the disease. In refractory cases, it may be necessary to use immunosuppressive treatments such as methotrexate, omalizumab or dupilumab [ 102 ]. ICI-induced vitiligo Vitiligo-like skin depigmentation may occur in 11% and 25% of patients with advanced melanoma receiving anti-CTLA-4 and anti-PD-1 therapy, respectively. The clinical phenotype of ICI-induced vitiligo involves multiple speckled macules that evolve into large spots located in sun-exposed areas. Sometimes, the lesions are preceded by previous erythema. Patients generally do not have a personal or family history of vitiligo or other autoimmune diseases. Severe cutaneous adverse reactions (SCARs) caused by targeted therapy and immunotherapy Targeted therapies and immune checkpoint inhibitors (ICIs) are associated with severe cutaneous adverse reactions (SCARs). These diseases are sub-classified as Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug reactions with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP). All these conditions represent severe skin conditions and may be associated with a high risk of mortality, highlighting the need for adequate early diagnosis and management. The appearance of systemic symptoms in a patient with a skin rash, especially if mucosal lesions or epidermal detachment appear, should alert physicians to a possible SCAR (Fig. 10 ). A recent study on AE notifications from the FDA (FAERS) revealed significant notification relative odds ratios (ROR) for SJS (ROR 7.3) and TEN (ROR 7.4) with a mortality rate of 55% in the case of TEN [ 103 ]. In general, SCARs have a low overall incidence in relation to targeted therapies; however, although cases involving almost all families of targeted therapy drugs have been reported, they are more common in treatment with EGFR, KIT, and BRAF inhibitors [ 104 ]. The association of DRESS and AGEP with targeted therapies is somewhat lower, with few cases described for various families, in particular KIT and BRAF inhibitors [ 105 ]. A recent systematic review revealed a greater association of DRESS than SJS-NET for BRAF-MEK inhibitors (with a ROR of 23 vs. 8), with vemurafenib being the most common drug [ 106 ]. Fig. 10 Full size image TEN (toxic epidermal necrolysis) secondary to nivolumab in a patient with stage IV melanoma. Extensive maculopapular exanthema (> 30% body area) with the presence of vesicles and blisters, as well as skin erosions and mucositis Grading of skin toxicity and recommendations for referral to a dermatologist Grading of cutaneous AEs AEs caused by cancer drugs, both in clinical trials and in clinical practice, are graded via the CTCAE, which was first developed in 1983 [ 107 ]. The current version (CTCAE v5.0) was published in November 2017 by the National Cancer Institute of the United States [ 108 ]. This document aims to offer a standardized description of the terms that allows an optimal exchange of information on the safety of antineoplastic therapies and the appropriate treatment of their AEs. The CTCAE v5.0 includes a series of signs, symptoms, and laboratory alterations attributed to antineoplastic therapies, in which a total of 47 dermatological AEs are included and graduated according to their severity via a 5-point scale ranging from Grade 1 (mild, asymptomatic, or few symptoms requiring only clinical observation without intervention or preventive treatment if available) to Grade 5 (death from AE) (Table 8 ). Table 8 General description of the recommended therapeutic approach to cutaneous toxicity according to the CTCAE v5.0 scale Full size table In 2011, the Multinational Association for Supportive Care in Cancer (MASCC) proposed the EGFR Inhibitor Skin Toxicity Tool (MESTT) as a specific classification system for each class of epidermal growth factor receptor (EGFR) inhibitors, including oral inhibitors of EGFR tyrosine kinase [ 109 , 110 ]. Although there appears to be a good correlation between CTCAE and MESTT, there is a tendency for MESTT to report more severe degrees of toxicity for some AEs, such as rash, xerosis, and paronychia [ 111 ]. However, this classification system has been developed specifically for EGFR inhibitors, with greater precision than CTCAE. The NCI Patient-Reported Outcomes-Common Terminology Criteria for AEs (PRO-CTCAE) system is an additional way to classify toxicities on the basis of information provided by patients. It complements the CTCAE, but its use has not yet spread widely [ 112 ]. There are other complementary classification models, such as the Adverse Drug Reaction Terminology of the World Health Organization (WHO-ART) or those of AEs issued by the Radiation Oncology Group (RTOG). In the first, the information is related to drugs, whereas the second covers all aspects of treatment, including radiotherapy, surgery, and drugs used [ 113 ]. While most international guidelines for the management of dermatological oncological toxicity [ 10 , 114 ] use CTCAE, this terminology has its limitations: as it has been mainly written by oncologists, some dermatological AEs (such as alopecia or blistering diseases) are covered in insufficient detail. Further efforts to integrate both disciplines are necessary to develop a more specific terminology for patients with cutaneous AEs due to targeted therapy. Recommendations for dermatologic referral and workup in cancer patients with cutaneous AEs Given the high prevalence and clinical impact of dermatologic AEs in oncology, timely referral to a dermatologist is essential for accurate diagnosis and optimal cancer patient management. Dermatology consultation improves cancer patient outcomes and minimizes unnecessary treatment modifications [ 115 ]. Referral to dermatology should be prioritized in cases of (1) failure of first-line therapy (e.g., topical corticosteroids or antihistamines); (2) atypical or evolving skin lesions where clinical diagnosis is uncertain; (3) need for skin biopsy or histopathologic characterization; (4) presence of pre-existing dermatologic diseases such as psoriasis, atopic dermatitis, or bullous disorders that may complicate cancer treatment; and (5) limited remaining treatment options when maintaining cancer treatment is critical [ 116 ]. Proactive dermatologic referral not only facilitates the differentiation between benign and potentially life-threatening skin reactions but also supports the safe and continued use of cancer therapies, even in complex cases. Dermatologists are essential partners in ensuring uninterrupted and effective oncologic treatment [ 3 ]. Moreover, recent advances in dermatologic immunomodulatory therapies have further expanded options for managing complex skin toxicities. Close collaboration between oncologists and dermatologists is essential to optimize both cancer outcomes and patient quality of life [ 117 ]. Conclusion Cutaneous toxicities derived from targeted therapies, ADCs, and immunotherapy are relatively frequent events presenting as a broad and heterogeneous clinical spectrum of AEs with significant impact on both patients’ quality of life and the continuity of anticancer treatment. Early identification of these reactions, their classification through standardized systems such as CTCAE v5.0, and the implementation of preventive and individualized therapeutic measures are key elements for effective management. The most common events—such as papulopustular eruptions, xerosis, hand–foot skin reactions, hair and nail alterations, photosensitivity, pigmentary disorders, and immune-mediated toxicities—should be interpreted not only as AEs, but also as biological expressions of the interaction between pharmacological mechanisms and skin biology. Understanding their pathophysiology allows optimization of prevention strategies (including photoprotection, gentle hygiene, emollients, prophylactic antibiotics, or specific hair and nail care) and tailoring of treatment according to severity, thereby avoiding unnecessary dose reductions or treatment discontinuations that could compromise oncologic efficacy. Accumulated experience shows that close and early collaboration between medical oncologists and dermatologists is fundamental to differentiate benign reactions from potentially life-threatening severe cutaneous adverse reactions (SCARs), and to ensure safe management in scenarios of comorbidity or complex toxicity. References Siegel RL, Kratzer TB, Giaquinto AN, Sung H, Jemal A. Cancer statistics, 2025. CA Cancer J Clin. 2025. https://doi.org/10.3322/caac.21871 . Article PubMed PubMed Central Google Scholar Geisler AN, Phillips GS, Barrios DM, Wu J, Leung DYM, Moy AP, et al. Immune checkpoint inhibitor–related dermatologic adverse events. J Am Acad Dermatol. 2020;83(5):1255–68. https://doi.org/10.1016/j.jaad.2020.03.132 . Article CAS PubMed PubMed Central Google Scholar Hackbarth M, Haas N, Fotopoulou C, Lichtenegger W, Sehouli J. Chemotherapy-induced dermatological toxicity: frequencies and impact on quality of life in women’s cancers. results of a prospective study. Support Care Cancer. 2008;16:267–73. https://doi.org/10.1007/s00520-007-0318-8 . Article PubMed Google Scholar Haynes D, Morgan EE, Chu EY. Cutaneous adverse reactions resulting from targeted cancer therapies: histopathologic and clinical findings. Hum Pathol. 2023;140:129–43. https://doi.org/10.1016/j.humpath.2023.04.014 . Article CAS PubMed Google Scholar Sibaud V. Dermatologic reactions to immune checkpoint inhibitors: skin toxicities and immunotherapy. Am J Clin Dermatol. 2018;19:345–61. https://doi.org/10.1007/S40257-017-0336-3 . Article PubMed Google Scholar Freites-Martinez A, Shapiro J, Goldfarb S, Nangia J, Jimenez JJ, Paus R, et al. Hair disorders in patients with cancer. J Am Acad Dermatol. 2019;80(5):1179–96. https://doi.org/10.1016/j.jaad.2018.03.055 . Article PubMed Google Scholar Okiyama N, Tanaka R. Immune-related adverse events in various organs caused by immune checkpoint inhibitors. Allergol Int. 2022;71(2):169–78. https://doi.org/10.1016/j.alit.2022.01.001 . Article CAS PubMed Google Scholar Suzuki Y, Zhou S, Ota Y, Harrington M, Miyagi E, Takagi H, et al. Toxicity profiles of antibody-drug conjugates for anticancer treatment: a systematic review and meta-analysis. JNCI Cancer Spectr. 2023. https://doi.org/10.1093/JNCICS/PKAD069 . Article PubMed PubMed Central Google Scholar 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;19:31–9. https://doi.org/10.1007/S40257-018-0384-3 . Article PubMed PubMed Central Google Scholar Lacouture ME, Sibaud V, Gerber PA, van den Hurk C, Fernández-Peñas P, Santini D, et al. Prevention and management of dermatological toxicities related to anticancer agents: ESMO clinical practice guidelines☆. Ann Oncol. 2021;32(2):157–70. https://doi.org/10.1016/j.annonc.2020.11.005 . Article CAS PubMed Google Scholar Stanculeanu DL, Zob D, Toma OC, Georgescu B, Papagheorghe L, Mihaila RI. Cutaneous Toxicities of Molecular Targeted therapies. Maedica (Bucur). 2017;12:48. PubMed PubMed Central Google Scholar Boone SL, Rademaker A, Liu D, Pfeiffer C, Mauro DJ, Lacouture ME. Impact and management of skin toxicity associated with anti-epidermal growth factor receptor therapy: survey results. Oncology. 2008;72:152–9. https://doi.org/10.1159/000112795 . Article CAS Google Scholar Deutsch A, Leboeuf NR, Lacouture ME, McLellan BN. Dermatologic adverse events of systemic anticancer therapies: cytotoxic chemotherapy, targeted therapy, and immunotherapy. Am Soc Clin Oncol Educ Book. 2020;40:485–500. https://doi.org/10.1200/EDBK_289911 . Article PubMed Google Scholar Sanmartín O. Skin manifestations of targeted antineoplastic therapy. Curr Probl Dermatol (Switzerland) S Karger AG. 2017;53:93–104. https://doi.org/10.1159/000479198 . Article Google Scholar Holcmann M, Sibilia M. Mechanisms underlying skin disorders induced by EGFR inhibitors. Mol Cell Oncol. 2015. https://doi.org/10.1080/23723556.2015.1004969 . Article PubMed PubMed Central Google Scholar Li Y, Fu R, Jiang T, Duan D, Wu Y, Li C, et al. Mechanism of lethal skin toxicities induced by epidermal growth factor receptor inhibitors and related treatment strategies. Front Oncol. 2022. https://doi.org/10.3389/FONC.2022.804212 . Article PubMed PubMed Central Google Scholar Qian J, Wan J, Yao Q, Chen Y, Ling T, Zhang Y, et al. Cutaneous adverse events associated with BRAF and MEK inhibitors: a systematic review and meta-analysis. Front Pharmacol. 2024. https://doi.org/10.3389/FPHAR.2024.1457226 . Article PubMed PubMed Central Google Scholar Sollena P, Vasiliki N, Kotteas E, Stratigos AJ, Fattore D, Orlandi A, 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 (Basel). 2023. https://doi.org/10.3390/CANCERS15143658 . Article PubMed PubMed Central Google Scholar Petrelli F, Ardito R, Ghidini A, Zaniboni A, Ghidini M, Barni S, et al. Different toxicity of cetuximab and panitumumab in metastatic colorectal cancer treatment: a systematic review and meta-analysis. Oncology. 2018;94:191–9. https://doi.org/10.1159/000486338 . Article CAS PubMed Google Scholar Lacouture ME, Anadkat M, Jatoi A, Garawin T, Bohac C, Mitchell E, et al. Dermatologic toxicity occurring during anti-EGFR monoclonal inhibitor therapy in patients with metastatic colorectal cancer: a systematic review. Clin Colorectal Cancer. 2018;17(2):85–96. https://doi.org/10.1016/J.CLCC.2017.12.004 . Article PubMed Google Scholar Santorsola M, Capuozzo M, Nasti G, Sabbatino F, Di Mauro A, Di Mauro G, et al. Exploring the spectrum of VEGF inhibitors’ toxicities from systemic to intra-vitreal usage in medical practice. Cancers (Basel). 2024. https://doi.org/10.3390/CANCERS16020350 . Article PubMed PubMed Central Google Scholar Basse C, Chabanol H, Bonte PE, Fromantin I, Girard N. Management of cutaneous toxicities under amivantamab (anti MET and anti EGFR bispecific antibody) in patients with metastatic non-small cell lung cancer harboring EGFR Exon20ins: towards a proactive, multidisciplinary approach. Lung Cancer. 2022;173:116–23. https://doi.org/10.1016/j.lungcan.2022.09.012 . Article CAS PubMed Google Scholar Gronbeck C, Hadfield MJ, Grant-Kels JM. Dermatologic toxicities of antibody-drug conjugates. J Am Acad Dermatol. 2024;91(6):1177–88. https://doi.org/10.1016/j.jaad.2024.08.036 . Article CAS PubMed Google Scholar 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;150:208–12. https://doi.org/10.1016/j.annder.2022.11.013 . Article CAS PubMed Google Scholar Mok TS, Wu Y-L, Thongprasert S, Yang C-H, Chu D-T, Saijo N, et al. Gefitinib or carboplatin–paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361:947–57. https://doi.org/10.1056/NEJMOA0810699 . Article CAS PubMed Google Scholar Shepherd F, Rodrigues Pereira J, Ciuleanu T, Huat Tan E, Hirsh V, Thonngprasert S, et al. Erlotinib in previously treated non–small-cell lung cancer. New Engl J Med. 2005;353:123–32. Article CAS PubMed Google Scholar Geyer CE, Forster J, Lindquist D. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. Adv Breast Cancer. 2008;5:45. https://doi.org/10.1056/NEJMOA064320 . Article Google Scholar Wu YL, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, et al. Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Lancet Oncol. 2017;18:1454–66. https://doi.org/10.1016/S1470-2045(17)30608-3 . Article CAS PubMed Google Scholar Chan A, Delaloge S, Holmes FA, Moy B, Iwata H, Harvey VJ, et al. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2016;17:367–77. https://doi.org/10.1016/S1470-2045(15)00551-3 . Article CAS PubMed Google Scholar Soria J-C, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, et al. Osimertinib in untreated EGFR -mutated advanced non–small-cell lung cancer. N Engl J Med. 2018;378(2):113–25. https://doi.org/10.1056/NEJMOA1713137 . Article CAS PubMed Google Scholar Uozumi S, Enokida T, Suzuki S, Nishizawa A, Kamata H, Okano T, et al. Predictive value of cetuximab-induced skin toxicity in recurrent or metastatic squamous cell carcinoma of the head and neck. Front Oncol. 2018. https://doi.org/10.3389/FONC.2018.00616 . Article PubMed PubMed Central Google Scholar Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol. 2008;26:1626–34. https://doi.org/10.1200/JCO.2007.14.7116 . Article CAS PubMed Google Scholar Yang JCH, Wu YL, Schuler M, Sebastian M, Popat S, Yamamoto N, et al. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 2015;16(2):141–51. https://doi.org/10.1016/S1470-2045(14)71173-8 . Article CAS PubMed Google Scholar Lichtenberger BM, Gerber PA, Holcmann M, Buhren BA, Amberg N, Smolle V, et al. Epidermal EGFR controls cutaneous host defense and prevents inflammation. Sci Transl Med. 2013. https://doi.org/10.1126/SCITRANSLMED.3005886 . Article PubMed Google Scholar Eilers RE, Gandhi M, Patel JD, Mulcahy MF, Agulnik M, Hensing T, et al. Dermatologic infections in cancer patients treated with epidermal growth factor receptor inhibitor therapy. J Natl Cancer Inst. 2010;102:47–53. https://doi.org/10.1093/JNCI/DJP439 . Article CAS PubMed Google Scholar Freites-Martinez A, Santana N, Arias-Santiago S, Viera A. Using the Common Terminology Criteria for Adverse Events (CTCAE – Version 5.0) to evaluate the severity of adverse events of anticancer therapies. Actas Dermosifiliogr. 2021;112:90–2. https://doi.org/10.1016/j.ad.2019.05.009 . Article CAS PubMed Google Scholar Perez-Soler R. Rash as a surrogate marker for efficacy of epidermal growth factor receptor inhibitors in lung cancer. Clin Lung Cancer. 2006. https://doi.org/10.3816/CLC.2006.s.008 . Article PubMed Google Scholar Jaka A, Gutiérrez-Rivera A, López-Pestaña A, del Alcázar E, Zubizarreta J, Vildosola S, et al. Predictors of tumor response to cetuximab and panitumumab in 116 patients and a review of approaches to managing skin toxicity. Actas Dermosifiliogr. 2015;106:483–92. https://doi.org/10.1016/J.ADENGL.2015.05.014 . Article CAS PubMed Google Scholar Petrelli F, Borgonovo K, Cabiddu M, Coinu A, Ghilardi M, Lonati V, et al. Antibiotic prophylaxis for skin toxicity induced by antiepidermal growth factor receptor agents: a systematic review and meta-analysis. Br J Dermatol. 2016;175:1166–74. https://doi.org/10.1111/BJD.14756 . Article CAS PubMed Google Scholar Sanmartin Jiménez O. Management of epidermal growth factor inhibitor-induced papulopustular rash: The dermatologist’s role. Actas Dermosifiliogr. 2015;106:447. Article PubMed Google Scholar Qi WX, Fu S, Zhang Q, Guo XM. Incidence and risk of severe infections associated with anti-epidermal growth factor receptor monoclonal antibodies in cancer patients: A systematic review and meta-analysis. BMC Med. 2014. https://doi.org/10.1186/S12916-014-0203-5 . Article PubMed PubMed Central Google Scholar Valentine J, Belum VR, Duran J, Ciccolini K, Schindler K, Wu S, et al. Incidence and risk of xerosis with targeted anticancer therapies. J Am Acad Dermatol. 2015;72:656–67. Article PubMed Google Scholar 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;17:387–402. https://doi.org/10.1007/S40257-016-0197-1 . Article PubMed Google Scholar Zhu Y, Zhang X, Lou X, Chen M, Luo P, He Q. Vascular endothelial growth factor (VEGF) antibody significantly increases the risk of hand–foot skin reaction to multikinase inhibitors (MKIs): A systematic literature review and meta-analysis. Clin Exp Pharmacol Physiol. 2018;45:659–67. https://doi.org/10.1111/1440-1681.12935 . Article CAS PubMed PubMed Central Google Scholar Lacouture ME, Reilly LM, Gerami P, Guitart J. Hand foot skin reaction in cancer patients treated with the multikinase inhibitors sorafenib and sunitinib. Ann Oncol. 2008;19:1955–61. https://doi.org/10.1093/annonc/mdn389 . Article CAS PubMed Google Scholar Belum VR, Serna-Tamayo C, Wu S, Lacouture ME. Incidence and risk of hand-foot skin reaction with cabozantinib, a novel multikinase inhibitor: A meta-analysis. Clin Exp Dermatol. 2016;41:8–15. https://doi.org/10.1111/CED.12694 . Article CAS PubMed Google Scholar McLellan B, Ciardiello F, Lacouture ME, Segaert S, Van Cutsem E. Regorafenib-associated hand-foot skin reaction: Practical advice on diagnosis, prevention, and management. Ann Oncol. 2015;26:2017–26. https://doi.org/10.1093/annonc/mdv244 . Article CAS PubMed PubMed Central Google Scholar Shou L, Chen J, Shao T, Zhang Y, Zhao S, Chen S, et al. Clinical characteristics, treatment outcomes, and prognosis in patients with MKIs-associated hand-foot skin reaction: a retrospective study. Support Care Cancer. 2023. https://doi.org/10.1007/S00520-023-07830-3 . Article PubMed Google Scholar Lu CW, Yeh CN, Hsu HC, Chen CB, Yang TS, Pan YR, et al. Zinc supplementation is associated with improvement in hand-foot skin reaction in patients on vascular endothelial growth factor receptor-tyrosine kinase inhibitors: A cohort study. J Am Acad Dermatol. 2024;90:814–5. https://doi.org/10.1016/j.jaad.2023.11.054 . Article CAS PubMed Google Scholar Nishizawa A, Shinozaki E, Wakatsuki T, Satoh T, Yamazaki N, Oyamada S, et al. Efficacy of aluminum chloride in severe regorafenib-associated hand-foot skin reactions: a single-arm trial. BMC Cancer. 2023. https://doi.org/10.1186/S12885-023-10864-9 . Article PubMed PubMed Central Google Scholar Mir-Bonafé JF, Saceda-Corralo D, Vañó-Galván S. Reacciones capilares de las nuevas terapias diana dirigidas contra el cáncer. Actas Dermosifiliogr. 2019;110:182–92. https://doi.org/10.1016/J.AD.2018.10.019 . Article PubMed Google Scholar Huynh Dagher S, Blom A, Chabanol H, Funck-Brentano E. Cutaneous toxicities from targeted therapies used in oncology: literature review of clinical presentation and management. Int J Womens Dermatol. 2021;7(5):615–24. https://doi.org/10.1016/J.IJWD.2021.09.009 . Article PubMed PubMed Central Google Scholar Rossi A, Pan A, Menzer C, Lavin L, Aleissa S, Aleisa A, et al. Platelet-Rich plasma treatment for endocrine-induced alopecia and persistent chemotherapy-induced alopecia in breast cancer survivors: a randomized, controlled, pilot study. Dermatol Surg. 2025. https://doi.org/10.1097/DSS.0000000000004755 . Article PubMed Google Scholar Antoury L, Maloney NJ, Bach DQ, Goh C, Cheng K. Alopecia areata as an immune-related adverse event of immune checkpoint inhibitors: A review. Dermatol Ther. 2020. https://doi.org/10.1111/DTH.14171 . Article PubMed Google Scholar Agrawal C, Goyal P, Doval Di, Dutta K, Domadia K, Kothiwal S. Eyelashes trichomegaly: an unusual side effect of gefitinib therapy. Int J Trichology. 2018;10:44–6. https://doi.org/10.4103/IJT.IJT_72_17 . Article PubMed PubMed Central Google Scholar Rivera N, Boada A, Bielsa MI, Fernández-Figueras MT, Carcereny E, Moran MT, et al. Hair repigmentation during immunotherapy treatment with an anti–programmed cell death 1 and anti–programmed cell death ligand 1 agent for lung cancer. JAMA Dermatol. 2017;153:1162–5. https://doi.org/10.1001/JAMADERMATOL.2017.2106 . Article PubMed PubMed Central Google Scholar Dika E, Patrizi A, Ribero S, Fanti PA, Starace M, Melotti B, et al. Hair and nail adverse events during treatment with targeted therapies for metastatic melanoma. Eur J Dermatol. 2016;26:232–9. https://doi.org/10.1684/EJD.2016.2747 . Article CAS PubMed Google Scholar 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. 2020;27:13030. Google Scholar George MN, Seervai RNH, Chon SY. Erosive pustular dermatosis-like eruption of the scalp secondary to amivantamab: a case series. JAAD Case Rep. 2024;47:72–9. https://doi.org/10.1016/j.jdcr.2023.11.027 . Article PubMed PubMed Central Google Scholar Cho BC, Girard N, Sauder MB, Feldman J, Li W, Bozorgmehr F, et al. P3.12D.04 enhanced vs standard dermatologic management with Amivantamab-Lazertinib in advanced NSCLC: Phase 2 COCOON Study. J Thorac Oncol. 2024;19:S347. https://doi.org/10.1016/J.JTHO.2024.09.626 . Article Google Scholar Garden BC, Wu S, Lacouture ME. The risk of nail changes with epidermal growth factor receptor inhibitors: a systematic review of the literature and meta-analysis. J Am Acad Dermatol. 2012;67:400–8. https://doi.org/10.1016/j.jaad.2011.10.009 . Article CAS PubMed Google Scholar Lacouture ME, Sibaud V, Anadkat MJ, Kaffenberger B, Leventhal J, Guindon K, et al. Dermatologic adverse events associated with selective fibroblast growth factor receptor inhibitors: overview, prevention, and management guidelines. Oncologist. 2021;26(2):e316–26. https://doi.org/10.1002/ONCO.13552 . Article Google Scholar Ho PH, Lin IC, Yang X, Cho YT, Chu CY. Using a novel scoring system for paronychia related to oncologic treatments (SPOT) for assessing paronychia severity and its correlation with pain index and quality of life. J Eur Acad Dermatol Venereol. 2019;33:204–12. https://doi.org/10.1111/JDV.15121 . Article PubMed Google Scholar Cubiró X, Planas-Ciudad S, Garcia-Muret MP, Puig L. Topical timolol for paronychia and pseudopyogenic granuloma in patients treatedwith epidermal growth factor receptor inhibitors and capecitabine. JAMA Dermatol. 2018;154:99–100. https://doi.org/10.1001/JAMADERMATOL.2017.4120 . Article PubMed PubMed Central Google Scholar Bodnar RJ. Anti-angiogenic drugs: involvement in cutaneous side effects and wound-healing complication. Adv Wound Care. 2014;3:635–46. https://doi.org/10.1089/WOUND.2013.0496 . Article Google Scholar Iwasa T, Adachi S, Ogiso H, Takada E, Mabuchi M, Suzuki Y, et al. Severe skin ulcer caused by taking lenvatinib after proton beam therapy. Clin J Gastroenterol. 2023;16:588–92. https://doi.org/10.1007/S12328-023-01802-0 . Article PubMed Google Scholar Martínez-Doménech Á, García-Legaz Martínez M, Pérez-Pastor G, Pérez-Ferriols A. Lenvatinib-associated late-onset necrosis of a radiated skin graft. J Dermatol. 2021;48:e267–8. https://doi.org/10.1111/1346-8138.15862 . Article CAS Google Scholar Jeon SH, Lee WJ, Won CH, Chang SE, Lee MW, Jung JM. Multiple lenvatinib-associated skin ulcers: a case report and literature review. Australas J Dermatol. 2023;64:e386–7. https://doi.org/10.1111/AJD.14162 . Article Google Scholar Samal A, Dixit N, Kar B, Mohapatra L. Tyrosine kinase inhibitors induced scrotal ulcerations: report of 2 cases. Indian J Dermatol. 2023;68(2):235. https://doi.org/10.4103/IJD.IJD_818_22 . Article PubMed PubMed Central Google Scholar Kuntz T, Koushk-Jalali B, Kreuter A. Sunitinib-induced pyoderma gangrenosum-like skin ulcer. CMAJ. 2020;192(20):552. https://doi.org/10.1503/CMAJ.191165 . Article Google Scholar Dai J, Belum VR, Wu S, Sibaud V, Lacouture ME. Pigmentary changes in patients treated with targeted anticancer agents: a systematic review and meta-analysis. J Am Acad Dermatol. 2017;77(5):902-910.e2. https://doi.org/10.1016/j.jaad.2017.06.044 . Article CAS PubMed PubMed Central Google Scholar Macdonald JB, Macdonald B, Golitz LE, LoRusso P, Sekulic A. Cutaneous adverse effects of targeted therapies: part I: inhibitors of the cellular membrane. J Am Acad Dermatol. 2015;72:203–18. https://doi.org/10.1016/j.jaad.2014.07.032 . Article CAS PubMed Google Scholar Hartmann JT, Kanz L. Sunitinib and periodic hair depigmentation due to temporary c-KIT inhibition. Arch Dermatol. 2008;144:1525–6. https://doi.org/10.1001/ARCHDERM.144.11.1525 . Article PubMed Google Scholar Vignand-Courtin C, Martin C, Le Beller C, Mateus C, Barbault-Foucher S, Rieutord A. Cutaneous side effects associated with sunitinib: an analysis of 8 cases. Int J Clin Pharm. 2012;34(2):286–9. https://doi.org/10.1007/S11096-012-9615-5 . Article PubMed Google Scholar Giacchero D, Ramacciotti C, Arnault JP, Brassard M, Baudin E, Maksimovic L, et al. A new spectrum of skin toxic effects associated with the multikinase inhibitor vandetanib. Arch Dermatol. 2012;148:1418–20. https://doi.org/10.1001/2013.JAMADERMATOL.192 . Article PubMed Google Scholar Hermann N, Maul LV, Ameri M, Traidl S, Ziadlou R, Papageorgiou K, et al. Clinical presentation and prognostic features in patients with immunotherapy-induced vitiligo-like depigmentation: a monocentric prospective observational study. Cancers (Basel). 2022. https://doi.org/10.3390/CANCERS14194576 . Article PubMed PubMed Central Google Scholar Cohen PR, Bedikian AY, Kim KB. Appearance of new vemurafenib-associated melanocytic nevi on normal-appearing skin: case series and a review of changing or new pigmented lesions in patients with metastatic malignant melanoma after initiating treatment with vemurafenib. J Clin Aesthet Dermatol. 2013;6:27–37. PubMed PubMed Central Google Scholar Lacouture ME, Duvic M, Hauschild A, Prieto VG, Robert C, Schadendorf D, et al. Analysis of dermatologic events in vemurafenib-treated patients with melanoma. Oncologist. 2013;18:314–22. https://doi.org/10.1634/THEONCOLOGIST.2012-0333 . Article CAS PubMed PubMed Central Google Scholar Morgado F, Calvão J, Barata F, Gonçalo M. Phototoxic reaction to brigatinib – a new photosensitizing drug. J Eur Acad Dermatol Venereol. 2019;33:e491–2. https://doi.org/10.1111/JDV.15818 . Article Google Scholar Ledermann JA, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, et al. Rucaparib for patients with platinum-sensitive, recurrent ovarian carcinoma (ARIEL3): post-progression outcomes and updated safety results from a randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2020;21(5):710–22. https://doi.org/10.1016/S1470-2045(20)30061-9 . Article CAS PubMed PubMed Central Google Scholar Wu J, Liu D, Offin M, Lezcano C, Torrisi JM, Brownstein S, et al. Characterization and management of ERK inhibitor associated dermatologic adverse events: analysis from a nonrandomized trial of ulixertinib for advanced cancers. Invest New Drugs. 2021;39:785–95. https://doi.org/10.1007/S10637-020-01035-9 . Article CAS PubMed PubMed Central Google Scholar Sakaguchi Y, Komori T, Aoki M, Otsuka A, Kabashima K, Matsushita S. Photosensitive dermatitis induced by nivolumab/ipilimumab combination therapy in a patient with malignant melanoma. Acta Derm Venereol. 2020;100:1–2. https://doi.org/10.2340/00015555-3681 . Article Google Scholar Caimi PF, Ai W, Alderuccio JP, Ardeshna KM, Hamadani M, Hess B, et al. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2021;22:790–800. https://doi.org/10.1016/S1470-2045(21)00139-X . Article CAS PubMed Google Scholar Sorensen EP, Thrush J, Bartlett NL, Rosman IS, Anadkat MJ, Jones HA. Diffuse telangiectatic rash associated with novel antibody drug conjugate therapies. JAMA Dermatol. 2020;156(5):601–3. https://doi.org/10.1001/JAMADERMATOL.2020.0208 . Article PubMed Google Scholar Sibaud V. Anticancer treatments and photosensitivity. J Eur Acad Dermatol Venereol. 2022;36:51–8. https://doi.org/10.1111/JDV.18200 . Article CAS PubMed PubMed Central Google Scholar Cebon JS, Flaherty K, Weber JS, Kim K, Infante JR, Daud A, et al. Comparison of BRAF inhibitor (BRAFi)-induced cutaneous squamous cell carcinoma (cuSCC) and secondary malignancies in BRAF mutation-positive metastatic melanoma (MM) patients (pts) treated with dabrafenib (D) as monotherapy or in combination with MEK1/2 inhibitor (MEKi) trametinib (T). J Clin Oncol. 2013;31:9016–9016. https://doi.org/10.1200/JCO.2013.31.15_SUPPL.9016 . Article Google Scholar Gibney GT, Messina JL, Fedorenko IV, Sondak VK, Smalley KSM. Paradoxical oncogenesis-the long-term effects of BRAF inhibition in melanoma. Nat Rev Clin Oncol. 2013;10:390–9. https://doi.org/10.1038/NRCLINONC.2013.83 . Article CAS PubMed PubMed Central Google Scholar Eroglu Z, Ribas A. Combination therapy with BRAF and MEK inhibitors for melanoma: latest evidence and place in therapy. Ther Adv Med Oncol. 2016;8:48–56. https://doi.org/10.1177/1758834015616934 . Article CAS PubMed PubMed Central Google Scholar Aggarwal P, Clark D, Shah A, Rismiller K, Neltner SA. Keratoacanthoma and cutaneous squamous cell carcinoma with PD-1 and PD-L1 inhibitor use. JAMA Dermatol. 2024;160(5):573–5. https://doi.org/10.1001/JAMADERMATOL.2024.0390 . Article PubMed PubMed Central Google Scholar Kong HH, Sibaud V, Chanco Turner ML, Fojo T, Hornyak TJ, Chevreau C. Sorafenib-induced eruptive melanocytic lesions. Arch Dermatol. 2008;144:820–2. https://doi.org/10.1001/ARCHDERM.144.6.820 . Article PubMed PubMed Central Google Scholar Zimmer L, Hillen U, Livingstone E, Lacouture ME, Busam K, Carvajal RD, et al. Atypical melanocytic proliferations and new primary melanomas in patients with advanced melanoma undergoing selective BRAF inhibition. J Clin Oncol. 2012;30:2375–83. https://doi.org/10.1200/JCO.2011.41.1660 . Article CAS PubMed PubMed Central Google Scholar Dalle S, Poulalhon N, Debarbieux S, Zaharia D, Mihm MC, Lacouture ME, et al. Tracking of second primary melanomas in vemurafenib-treated patients. JAMA Dermatol. 2013;149:488–90. https://doi.org/10.1001/JAMADERMATOL.2013.21 . Article CAS PubMed Google Scholar Gounder M, Ratan R, Alcindor T, Schöffski P, van der Graaf WT, Wilky BA, et al. Nirogacestat, a γ-secretase inhibitor for desmoid tumors. N Engl J Med. 2023;388(10):898–912. https://doi.org/10.1056/NEJMOA2210140 . Article CAS PubMed PubMed Central Google Scholar Chen ST, Semenov YR, Alloo A, Bach DQ, Betof Warner A, Bougrine A, et al. Defining D-irAEs: consensus-based disease definitions for the diagnosis of dermatologic adverse events from immune checkpoint inhibitor therapy. J Immunother Cancer. 2024. https://doi.org/10.1136/JITC-2023-007675 . Article PubMed PubMed Central Google Scholar CTEP Trial Development and Conduct - NCI . [cited 2025 Aug 28]. https://dctd.cancer.gov/research/ctep-trials/trial-development . Accessed 28 Aug 2025 Spain L, Diem S, Larkin J. Management of toxicities of immune checkpoint inhibitors. Cancer Treat Rev. 2016;44:51–60. https://doi.org/10.1016/j.ctrv.2016.02.001 . Article CAS PubMed Google Scholar Phillips GS, Wu J, Hellmann MD, Postow MA, Rizvi NA, Freites-Martinez A, et al. Treatment outcomes of immune-related cutaneous adverse events. J Clin Oncol. 2019;37:2746–58. https://doi.org/10.1200/JCO.18.02141 . Article CAS PubMed PubMed Central Google Scholar Puzanov I, Diab A, Abdallah K, Bingham CO, Brogdon C, Dadu R, et al. Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) toxicity management working group. J Immunother Cancer. 2017. https://doi.org/10.1186/S40425-017-0300-Z . Article PubMed PubMed Central Google Scholar Shi VJ, Rodic N, Gettinger S, Leventhal JS, Neckman JP, Girardi M, 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;152:1128–36. https://doi.org/10.1001/JAMADERMATOL.2016.2226 . Article PubMed PubMed Central Google Scholar Halle BR, Betof Warner A, Zaman FY, Haydon A, Bhave P, Dewan AK, et al. Immune checkpoint inhibitors in patients with pre-existing psoriasis: safety and efficacy. J Immunother Cancer. 2021. https://doi.org/10.1136/JITC-2021-003066 . Article PubMed PubMed Central Google Scholar Sadik CD, Langan EA, Gutzmer R, Fleischer MI, Loquai C, Reinhardt L, et al. Retrospective analysis of checkpoint inhibitor therapy-associated cases of bullous pemphigoid from six German dermatology centers. Front Immunol. 2021. https://doi.org/10.3389/FIMMU.2020.588582 . Article PubMed PubMed Central Google Scholar Planella-Fontanillas N, Bosch-Amate X, Antón AJ, Moreno-Vílchez C, Guerrero MG, Blanes Martínez MdelM, et al. Real-world evaluation of the effectiveness and safety of dupilumab in bullous pemphigoid: an ambispective multicentre case series. Br J Dermatol. 2025;192:501–9. https://doi.org/10.1093/BJD/LJAE403 . Article CAS PubMed Google Scholar Godfrey H, Jedlowski P, Thiede R. Severe cutaneous adverse reactions associated with the immune checkpoint inhibitors: a case/non-case analysis using the Food and Drug Administration Adverse Event Reporting System. Australas J Dermatol. 2024;65:243–53. https://doi.org/10.1111/AJD.14262 . Article PubMed Google Scholar Ng CY, Chen CB, Wu MY, Wu J, Yang CH, Hui RCY, et al. Anticancer drugs induced severe adverse cutaneous drug reactions: an updated review on the risks associated with anticancer targeted therapy or immunotherapies. J Immunol Res. 2018. https://doi.org/10.1155/2018/5376476 . Article PubMed PubMed Central Google Scholar Chen CB, Wu MY, Ng CY, Lu CW, Wu J, Kao PH, et al. Severe cutaneous adverse reactions induced by targeted anticancer therapies and immunotherapies. Cancer Manag Res. 2018;10:1259–73. https://doi.org/10.2147/CMAR.S163391 . Article CAS PubMed PubMed Central Google Scholar Torres-Navarro I, de Unamuno-Bustos B, Botella-Estrada R. Systematic review of BRAF/MEK inhibitors-induced severe cutaneous adverse reactions (SCARs). J Eur Acad Dermatol Venereol. 2021;35:607–14. https://doi.org/10.1111/JDV.16894 . Article CAS PubMed Google Scholar Miller TP, Fisher BT, Getz KD, Sack L, Razzaghi H, Seif AE, et al. Unintended consequences of evolution of the Common Terminology Criteria for Adverse Events. Pediatr Blood Cancer. 2019;66:e27747. https://doi.org/10.1002/pbc.27747 . Article PubMed PubMed Central Google Scholar U.S. Department of Health and Human Services (2017) Common Terminology Criteria for Adverse Events (CTCAE) v.5.0. Cancer Therapy Evaluation Program (CTEP). 155. Lacouture ME, Maitland ML, Segaert S, Setser A, Baran R, Fox LP, et al. A proposed EGFR inhibitor dermatologic adverse event-specific grading scale from the MASCC skin toxicity study group. Support Care Cancer. 2010;18:509–22. https://doi.org/10.1007/s00520-009-0744-x . Article PubMed Google Scholar https://mascc.org/wp-content/uploads/2022/04/mestt.pdf . Chan A, Tan EH. How well does the MESTT correlate with CTCAE scale for the grading of dermatological toxicities associated with oral tyrosine kinase inhibitors? Support Care Cancer. 2011;19:1667–74. https://doi.org/10.1007/s00520-010-0999-2 . Article PubMed Google Scholar Gu S, Menzer C, Hay JL, Pena C, Dusza S, Lacouture ME, et al. PRO-CTCAE reveals under-recognition of dermatologic symptom burden in hospitalized cancer patients. Support Care Cancer. 2023;31:337. https://doi.org/10.1007/s00520-023-07793-5 . Article PubMed PubMed Central Google Scholar https://who-umc.org/whodrug/ Haanen J, Obeid M, Spain L, Carbonnel F, Wang Y, Robert C, et al. Management of toxicities from immunotherapy: ESMO clinical practice guideline for diagnosis, treatment and follow-up ☆. Ann Oncol. 2022;33:1217–38. https://doi.org/10.1016/j.annonc.2022.10.001 . Article CAS PubMed Google Scholar Kwong BY. Outcomes of embedding dermatologic care within oncology practices for patients with cancer. JAMA Dermatol. 2020;156:1051–2. https://doi.org/10.1001/JAMADERMATOL.2020.1794 . Article PubMed Google Scholar Fattore D, Lauletta G, Apalla Z, Sibaud V, Freites-Martinez A. Dermatologic immune-related adverse events: it is time for a game change! J Eur Acad Dermatol Venereol. 2025;39:e271–2. https://doi.org/10.1111/JDV.20282 . Article PubMed Google Scholar Freites-Martinez A, Apalla Z, Fattore D, Fida M, Bang AS, Smith J, et al. Supportive oncodermatology practices in Europe and the USA. J Eur Acad Dermatol Venereol. 2024;38(5):e440–3. https://doi.org/10.1111/JDV.19679 . Article PubMed Google Scholar Yang Z, Hackshaw A, Feng Q, Fu X, Zhang Y, Mao C, et al. Comparison of gefitinib, erlotinib and afatinib in non-small cell lung cancer: a meta-analysis. Int J Cancer. 2017;140:2805–19. https://doi.org/10.1002/IJC.30691 . Article CAS PubMed Google Scholar Download references Acknowledgements The authors are grateful for the editorial assistance of Bernadette Pfang, on behalf of Springer Health+, in the production of this manuscript. The Spanish Society of Medical Oncology (SEOM) and the Spanish Academy of Dermatology and Venereology (AEDV) are grateful for financial support for this project in the form of unrestricted grants from Johnson&Johnson and La Roche Posay. Funding This medical writing assistance was funded by the Spanish Society of Medical Oncology (SEOM) and the Spanish Academy of Dermatology and Venereology (AEDV) with an unrestricted grant from Johnson & Johnson and La Roche Posay. Author information Author notes Kevin Molina Mata, Ander Mayor Ibarguren, Marta Zafra Poves, Celia Requena, Francisco de Asis Aparisi Aparisi, Cristina Carrera, Ana Blasco Cordellat, Azael Freites-Martinez authors are contributed equally. Authors and Affiliations Medical Oncology Department, Hospital de La Santa Creu I Sant Pau, Barcelona, Spain Margarita Majem Medical Oncology Department, Institut Català D’Oncologia (ICO), Barcelona, Spain Kevin Molina Mata Dermatology Department, Hospital La Paz, Madrid, Spain Ander Mayor Ibarguren Medical Oncology Department, Hospital Universitario Morales Meseguer, Murcia, Spain Marta Zafra Poves Dermatology Department, Fundación Instituto Valenciano de Oncología, Valencia, Spain Celia Requena & Onofre Sanmartin Medical Oncology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain Francisco de Asis Aparisi Aparisi Dermatology Department, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain Cristina Carrera Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto Salud Carlos III, Madrid, Spain Cristina Carrera Medical Oncology Department, Hospital Ascires, Valencia, Spain Ana Blasco Cordellat Dermatology Department, Hospital Ruber Juan Bravo, Universidad Europea, Madrid, Spain Azael Freites-Martinez Authors Margarita Majem View author publications Search author on: PubMed Google Scholar Kevin Molina Mata View author publications Search author on: PubMed Google Scholar Ander Mayor Ibarguren View author publications Search author on: PubMed Google Scholar Marta Zafra Poves View author publications Search author on: PubMed Google Scholar Celia Requena View author publications Search author on: PubMed Google Scholar Francisco de Asis Aparisi Aparisi View author publications Search author on: PubMed Google Scholar Cristina Carrera View author publications Search author on: PubMed Google Scholar Ana Blasco Cordellat View author publications Search author on: PubMed Google Scholar Azael Freites-Martinez View author publications Search author on: PubMed Google Scholar Onofre Sanmartin View author publications Search author on: PubMed Google Scholar Contributions All authors participated in the drafting and critical review of the manuscript and gave final approval of the version to be published. Corresponding author Correspondence to Margarita Majem . Ethics declarations Conflicts of interest MM reports honoraria from Amgen, AstraZeneca, Roche, Bristol Myers Squibb, Merck Sharp & Dohme, Pfizer, Boehringer Ingelheim, Novartis, Immedica, Helsinn Therapeutics, Takeda, Sanofi, Johnson & Johnson, Pierre Fabre, Beigene, Lilly; Research Funding from Bristol-Myers Squibb (Inst), AstraZeneca (Inst), Roche (Inst); travel, accommodations from AstraZeneca, Roche, Pfizer, MSD, Johnson & Johnson. FdAAA reports holding a consultant role at Pfizer and Boehringer Inghelheim, being a speaker for Astra Zeneca, Takeda, and Sanofi, receiving travel expenses from Janssen, Gallecto, Pfizer, Roche, MSD, and Takeda; and others (GIDO). CC reports having received honoraria for speaking for La Roche Posay, ISD, Jonhson and Johnson, as well as travel grants from SANOFI, Pierre Fabre, ISDIN, and BMS. AF-M received support for attending meetings and/or travel from J&J Spain, ISDIN Spain, Galderma Spain; consultancy from SHB Law Firm–Sanofi; and honoraria/educational support from J&J Spain, ISDIN Spain, Galderma Spain, and SHB Law Firm–Sanofi. OS reports being a consultant for Johnson and Johnson, Regeneron, Roche Pharma, Sunpharma and Cantabria Labs. ABC, AMI, KMM, CR, and MZP, have no conflicts of interest to disclose. Informed consent All patients gave informed consent for the publication of their images that illustrate this article. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. 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To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/ . Reprints and permissions About this article Cite this article Majem, M., Molina Mata, K., Mayor Ibarguren, A. et al. Diagnosis and treatment of cutaneous adverse effects of targeted therapy, antibody–drug conjugates, and immunotherapy in cancer patients: a national consensus statement by the Spanish Society of Medical Oncology and the Spanish Academy of Dermatology and Venereology. Clin Transl Oncol 28 , 2603–2624 (2026). https://doi.org/10.1007/s12094-025-04209-0 Download citation Received : 19 December 2025 Accepted : 22 December 2025 Published : 28 January 2026 Version of record : 28 January 2026 Issue date : July 2026 DOI : https://doi.org/10.1007/s12094-025-04209-0 Share this article Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. 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