Clinical associations and classification of immune checkpoint inhibitor-induced cutaneous toxicities: a multicentre study from the European Academy of Dermatology and Venereology Task Force of Dermatology for Cancer Patients.

BACKGROUND: Cutaneous immune-related adverse events (irAEs) represent the most frequent toxicities induced by immune checkpoint inhibitors (ICIs). OBJECTIVES: To investigate clinical associations of cutaneous toxicities induced by different ICI therapies. METHODS: This was a multicentre retrospective international cohort study of patients with cancer who developed cutaneous irAEs under ICI therapy. Analysis was performed of the rates and basic characteristics of all cutaneous toxicities, and identification of any associations was performed using univariate and multivariate models. RESULTS: In total, 762 patients were included, who developed 993 cutaneous toxicities. Forty different types of skin toxicities were identified. Psoriasis (175 patients, 23·0%) and pruritus (171 patients, 22·4%) were the most common toxicities, followed by macular rash (161 patients, 21·1%) and eczematous-type reactions (150 patients, 19·7%). Multivariate analysis showed that among patients with macular rash, vitiligo or multiple toxicities, patients received ICIs more frequently for melanoma than for NSCLC. Moreover, anti-CTLA4 was less frequent than anti-programmed death 1 treatment in patients with macular rash [odds ratio (OR) 0·11, 95% confidence interval (CI) 0·01-0·76] and vitiligo (OR 0·07, 95% CI 0·006-0·78). A significant association was also seen in patients treated with a combination of ICI and chemotherapy vs. ICI monotherapy. They less frequently developed psoriasis (OR 0·08, 95% CI 0·02-0·31), lichenoid reactions (OR 0·15, 95% CI 0·03-0·77) and eczematous reactions (OR 0·24, 95% CI 0·07-0·78), all compared with pruritic rash. CONCLUSIONS: Our study showed that skin-oriented toxicities do not share a single pattern and are related to several factors, including the specific agent administered and the underlying malignancy treated. Follow-up plans should be individualized in order to minimize the risk for severe reactions that could compromise optimum therapeutic outcome. What is already known about this topic? Patients with cancer treated with different immune checkpoint inhibitors (ICIs) carry an increased risk of developing various types of skin toxicities. What are the clinical implications of this work? In this multicentre cohort study we showed that ICI-related skin toxicities do not share a single pattern and may depend on several factors, including the specific agent administered and the underlying malignancy. Among patients with macular rash, vitiligo or multiple skin toxicities, patients received ICIs more frequently for melanoma than for non-small cell lung cancer. The combination of ICI and chemotherapy compared with ICI monotherapy occurred to a lesser extent in patients with psoriatic rash lichenoid and eczematous reactions, compared with patients with pruritus. Clinical awareness and specialized dermatological consultation should be advocated.

Melanoma: new insights and new therapies.

Metastatic melanoma has historically been considered as one of the most therapeutically challenging malignancies. However, for the first time after decades of basic research and clinical investigation, new drugs have produced major clinical responses. The discovery of BRAF mutations in melanoma created the first opportunity to develop oncogene-directed therapy in this disease and led to the development of compounds that inhibit aberrant BRAF activity. A decade later, vemurafenib, an orally available and well-tolerated selective BRAF inhibitor, ushered in a new era of molecular treatments for advanced disease. Additional targets have been identified, and novel agents that impact on various signaling pathways or modulate the immune system hold the promise of a whole new therapeutic landscape for patients with metastatic melanoma. One of the major thrusts in melanoma therapy is now focused on understanding and targeting the network of signal transduction pathways and on attacking elements that underlie the tumor's propensity for growth and chemoresistance. In this article, we review the novel targeted anticancer approaches that are under consideration in melanoma treatment.

Risk associations of melanoma in a Southern European population: results of a case/control study.

OBJECTIVES: Limited data exist about the risk factors of melanoma in the Greek population. We investigated the association of melanoma with phenotypic and solar indices in this darker skin population residing in an environment of high ambient ultraviolet radiation. METHODS: Our study included 200 sporadic melanoma cases and 200 age-, sex-matched control subjects. Information on history of sun exposure patterns and cutaneous reaction to sunlight was obtained and a clinical evaluation of pigmentary traits, pigmented lesions, and actinic keratoses was performed. RESULTS: In the multivariate analysis, fair skin (OR: 4.63, for fair skin versus light brown, 95% CI: 1.54-13.92), intermittent sun exposure during childhood (OR: 3.33, >2 weeks/year of sun exposure versus < or =2 weeks/year 95% CI: 1.37-8.09), and outdoor leisure activities (OR: 2.74, 95% CI: 1.28-5.89), but not skin phototype or sunburns, were positively related to the risk of melanoma. In addition to an elevated count of common melanocytic nevi (OR: 6.27, > or =10 nevi versus no nevi, 95% CI: 1.65-23.76) and the presence of clinically atypical nevi (OR: 2.84, 95% CI: 1.16-6.98), solar lentigenes were an independent risk factor of melanoma (OR: 4.33, 95% CI: 1.67-11.22). CONCLUSIONS: Intermittent sun exposure of moderate intensity during childhood/adolescence and outdoor leisural activities, in conjunction with a more resistant skin phenotype to acute sunburns and a strong association with nevi and solar lentigenes was a prominent determinant of melanoma risk in our population.

Nonablative skin rejuvenation.

Laser resurfacing of photodamaged or scarred skin has traditionally involved the use of ablative lasers with their associated limitations and side effects. Nonablative skin rejuvenation is a relatively new concept in facial rejuvenation, which aims to induce dermal remodeling without visible epidermal disruption. A number of laser devices and light sources, emitting at various wavelengths, have been shown to effectively enhance the appearance of facial skin through nonablative mechanisms. Among the conditions that can be treated with this novel modality are erythema, telangiectasia, pigmentation, lentigines, and textural imperfections ranging from fine and moderate rhytides to other surface irregularities such as acne scarring. A major attraction of nonablative laser therapy is the very limited downtime after each treatment, making it an ideal method for patients seeking a minimally invasive procedure with an excellent safety profile.