Unaddressed Challenges in the Treatment of Cutaneous Melanoma?

Background and Objectives: While the management of noninvasive cutaneous melanoma (CM) is typically limited to a secondary excision to reduce recurrence risk and periodic follow-up, treating patients with advanced melanoma presents ongoing challenges. Materials and Methods: This review provides a comprehensive examination of both established and emerging pharmacologic strategies for advanced CM management, offering an up-to-date insight into the current therapeutic milieu. The dynamic landscape of advanced CM treatment is explored, highlighting the efficacy of immune checkpoint inhibitors and targeted therapies, either in monotherapy or combination regimens. Additionally, ongoing investigations into novel treatment modalities are thoroughly discussed, reflecting the evolving nature of melanoma management. Results: The therapeutic landscape for melanoma management is undergoing significant transformation. Although various treatment modalities exist, there remains a critical need for novel therapies, particularly for certain stages of melanoma or cases resistant to current options. Conclusions: Consequently, further studies are warranted to identify new treatment avenues and optimize the utilization of existing drugs.

Efficacy and Safety of Cemiplimab for the Management of Non-Melanoma Skin Cancer: A Drug Safety Evaluation.

Non-melanoma skin cancer includes several types of cutaneous tumors, with basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) as the commonest. Among the available therapeutic options, surgical excision is the mainstay of treatment for both tumors. However, tumor features and patients' comorbidities may limit the use of these techniques, making the treatment challenging. As regards BCC, even if hedgehog inhibitors revolutionized the therapeutic scenario, there are still patients unresponsive or intolerant to these drugs. In this context, cemiplimab has been approved as second-line treatment. As regards SCC, cemiplimab was the first systemic therapy approved. The objective of this manuscript was to investigate the efficacy and safety of cemiplimab for the management of BCC and cSCC. Cemiplimab has a durable and significant effect for the management of BCC and CSCC, with a favorable safety profile. Different specialists including oncologists, radiologists, dermatologists, and surgeons are required to guarantee an integrated approach, leading to the best management of patients. Moreover, the collaboration among specialists will allow them to best manage the TEAEs, reducing the risk of treatment suspension or discontinuation. Certainly, ongoing studies and more and more emerging real-world evidence, will allow us to better characterize the role of cemiplimab for the management of advanced non-melanoma skin cancer.

Biological Therapy for Psoriasis in Cancer Patients: An 8-Year Retrospective Real-Life Study.

Background: It is now recognized that psoriasis plays a key role in the development of several comorbidities, such as cardiovascular disease, and metabolic syndrome. Some authors have hypothesized that patients with psoriasis may have an increased risk of developing certain types of cancer. The efficacy and safety of biologic drugs are well-documented in clinical trials and in real-life studies. However, there is limited evidence on the safety of the use of biologic treatments in cancer patients with psoriasis, and the use of this therapeutic class in patients with a pre-existing or concomitant malignancy is still debated. Methods: We have conducted a retrospective observational study of a group of oncology patients with moderate-to-severe psoriasis treated with biologic therapy at the Dermatology Clinic of the University of Naples Federico II, during the period from 2016 to 2024. We included 20 adult patients; in 15 of them the diagnosis of neoplasm preceded the start of treatment biologic, while four of these patients had been diagnosed with cancer during the course of therapy biologics. Results: The most represented neoplasms in our population were breast carcinoma, prostate carcinoma, thyroid carcinoma, and chronic lymphatic leukemia. Anti-IL17 drugs were the most frequently prescribed (47.7%), followed by anti-IL23p19 (36.8%), anti-IL-12/23 (10.5%) and anti-TNF alpha (5.26%). All patients showed improvement of psoriasis after starting the therapy. Conclusions: Our experience supports the effectiveness and safety of biological therapy for psoriasis in patients with a history of cancer or recent onset neoplasia.

Secukinumab in Hidradenitis Suppurativa Patients Who Failed Adalimumab: A 52-Week Real-Life Study.

Background: The treatment of hidradenitis suppurativa (HS) has always been a real challenge for dermatologists; to date, adalimumab the only biologic drug approved for HS is adalimumab, an anti-tumor necrosis factor (TNF)-α drug, the approval of this drug dates to 2015, data provided by real life show an effectiveness rate of about 60% percent. Recently (31 October 2023) FDA approves secukinumab for moderate-severe HS. The treatment and management of HS is very challenging as available treatments are very limited and show very variable outcomes. Methods: We conducted a prospective monocentric study designed to evaluate the efficacy and safety of secukinumab treatment in HS patients in a real-life setting. Results: The initial cohort of patients recruited included 21 HS patients including 12 females and 9 males. About 57.1% of patients achieved the primary endpoint and recorded significant decrease in all the severity assessment scales (IHS4, DLQI and VAS pain scale) at week 16 and 52, when HiSCR reached 71.4%. Conclusion: The results of our study highlight that treatment with secukinumab in patients with severe HS who failed adalimumab may be a safe and effective therapeutic weapon.

Topical 5-aminolevulinic acid (ALA)-photodynamic therapy (PDT) for lichen sclerosus of face: case report and literature review.

Lichen sclerosus (LS) is a chronic inflammatory dermatosis typical of the genital region, with rare involvement of extragenital areas and particularly the face. LS therapeutic management is challenging, and common therapies including topical and systemic corticosteroids, topical calcineurin inhibitors, surgery are often ineffective. Herein, we present a case of LS occurred in a 36-year-old girl with facial involvement resistant to therapy with systemic corticosteroids and topical tacrolimus. Considering the involvement of a sensitive area, the young age of the patient, and the consistent clinical experience in using photodynamic therapy for the treatment of facial skin disease, we started a treatment with topical 5-aminolevulinic acid (ALA)-photodynamic therapy (PDT) with a dosage of 37 J/cm2 once a month. We compared our case with eight other facial LS patients from the literature and treated differently.

An update on the current and emerging pharmacotherapies for basal cell carcinomas.

INTRODUCTION: Despite surgical approach is still the mainstay for basal cell carcinoma (BCC) management, several issues may limit the use of this technique, leading to the need for new treatments to offer patients a personalized approach. AREAS COVERED: A comprehensive review of the available and emerging pharmacologic strategies for BCC management, including mechanisms of action, and potential adverse effects, has been performed to provide with an up-to-date manuscript on the current treatment scenario of BCC. Globally, targeting the Sonic-Hedgehog pathway is one of the main mechanisms of action of currently investigated drugs. Other alternatives are based on the concept of an enhancement of the immune response such as immune checkpoint inhibitors, or intra-tumor treatments. EXPERT OPINION: Although low-risk BCCs are often treated with destructive methods or topical treatments, surgery is the mainstay of treatment for the majority of BCCs. However, several factors may limit the use of surgery in BCC management. Recently, major knowledge on BCCs pathogenesis has led to the development of effective and selective drugs. In our opinion, soon many drugs will be licensed, allowing clinicians to offer patients with BCC the right treatment at the right moment. Certainly, further studies are needed.

Guselkumab, Risankizumab, and Tildrakizumab in the Management of Hidradenitis Suppurativa: A Review of Existing Trials and Real-Life Data.

The treatment of hidradenitis suppurativa (HS) has always been a real challenge for dermatologists; to date, the only biologic drugs approved for HS are adalimumab, an anti-tumor necrosis factor (TNF)-α drug, authorized in 2015, and secukinumab, recently licensed. The management of this condition is challenging as the available treatments show variable results, and the course of the condition is often chronic-recurrent; therefore, it will be necessary for the future to identify new therapeutic targets for HS. In recent years, studies have focused on the development towards new therapeutic targets. The purpose of our review was to perform a comprehensive literature review of real-life data on anti-IL23 (guselkumab, tildrakizumab, and risankizumab) in HS to summarize the existing evidence on the efficacy and safety of these drugs. We selected 64 articles, among which 32 had the characteristics that we were looking for in our review. To date, the positive data expressed in real-life experiences contrast with the three existing Phase 2 studies conducted so far, where it seems that these drugs may be useful only for a subgroup of patients with HS whose features need to be elucidated. Data from Phase 3 studies and other real-life experiences, perhaps more detailed and with higher numbers, will certainly be needed to fully understand the efficacy and safety of this class of drugs.

Development of a Patient-Reported Outcome Measure (PROM) for Dysgeusia During Treatment With Smoothened (SMO) Inhibitors for Basal Cell Carcinomas: The SMO-iD Questionnaire.

INTRODUCTION: Dysgeusia may occur during conventional or target-therapies and affect patients adherence-to-treatment. Therefore, it should be monitored to improve clinical outcome. To date, available questionnaires on dysgeusia relate to traditional antineoplastics and do not apply to target-therapies as the pathogenetic mechanism and clinical expression differ. OBJECTIVES: To develop a patient-reported outcome measure (PROM) to screen for and monitor the occurrence and severity of dysgeusia in patients under Smoothened (SMO) inhibitors: the SMO-iD questionnaire. METHODS: Patients with locally advanced basal cell carcinomas referring dysgeusia under SMO inhibitors at the University Hospital of Naples Federico II, were enrolled between January-December 2020. The PROM was elaborated based on chemotherapy-induced dysgeusia (CiTas) scale (development phase) and then validated by measuring internal consistency and reliability (validation phase). RESULTS: Thirty-nine patients were enrolled and interviewed every 8 weeks. In the first phase, 160 CiTas questionnaires were collected, and the SMO-iD questionnaire was developed. In the second phase, 195 SMO-iD questionnaires were recorded, and reliability and validity assessed. Cronbach alpha was 0.89. CONCLUSIONS: The SMO-iD questionnaire is a validated questionnaire that shows high face and content validity as well as high internal consistency and reliability. Hence, it may be introduced in daily clinical setting to monitor dysgeusia in patients under SMO-inhibitors.

The Efficacy of Sonidegib in Treating Locally Advanced Basal Cell Carcinoma Involving the Periocular Area.

INTRODUCTION: Basal cell carcinoma (BCC) is the most common skin malignancy in Caucasians. Globally, about 20% of BCCs involve the periocular region. The treatment of periocular BCC may be very challenging because of its proximity to the intracranial structures. Thus, early diagnosis and early treatment is mandatory. Recently, the introduction of Hedgehog pathway inhibitor therapy revolutionized the management of unresectable BCCs. The aim of our study was to evaluate the outcome of sonidegib treatment in patients affected by periocular locally advanced (la) BCC at our skin cancer center. METHODS: A 3-year retrospective study was carried out enrolling patients with periocular laBCC treated with sonidegib. Therapeutic response was defined as complete remission (CR) in case of complete regression of the tumor, partial remission (PR) in case of tumor regression not achieving complete remission, and stable disease (SD). RESULTS: A total 16 patients (11 men and 5 women; medium age 71.6 ± 11.5 years) with periocular laBCCs undergoing treatment with 200 mg/day of sonidegib were included in our study. Patients included in the study were treated for at least 6 months for a median duration of 9 months. Overall, CR was reported in 9/16 (56.2%) patients, PR was reported in 4/16 patients (25%), and tumor remained stable in 3 patients (18.8%). No cases of disease progression were collected. Fourteen out of 16 patients experienced multiple adverse events (AEs): dysgeusia was reported in 12 (75%) patients, muscle spasms in 13 (81%) patients, and 7 (43.7%) patients presented with alopecia. However, all of the AEs were mild and none required treatment discontinuation. CONCLUSION: To the best of our knowledge, this is the first study investigating the effectiveness and safety of sonidegib in the management of BCC localized at the periocular region. Even if limited, our study suggests this drug as a valuable and safe option in periocular BCC management.

Nail Psoriasis: An Updated Review of Currently Available Systemic Treatments.

Background: Nail psoriasis (NP) has a prevalence that ranges from 10 to 82% among patients with psoriasis (PsO) and is one of the most common difficult to treat site of psoriasis. We performed a thorough review of the literature, exploring evidence regarding all available NP systemic treatments, describing also in detail NP dedicated clinical trials. Methods: A literature search was conducted in PubMed and Embase prior to February 2023 using a combination of the terms "nail" AND "psoriasis" AND "systemic therapy" AND/OR "systemic treatment". A total of 47 original studies and case reports were reviewed in this article. Results: Systemic therapies should be considered when the disorder involves more than 3 nails, has extensive skin and joint involvement, and has a significant impact on QoL, due to their best long-term efficacy. In detail, conventional and biologic systemic drugs demonstrated efficacy in recent trials, including acitretin, methotrexate, cyclosporine, apremilast, adalimumab, infliximab, etanercept, certolizumab, golimumab, ustekinumab, secukinumab, ixekizumab, brodalumab, bimekizumab, guselkumab, risankizumab and tildrakizumab. Conclusion: Several therapies have demonstrated efficacy and safety in the treatment of NP; however, the choice of treatment depends not only on the severity of the nail involvement, but also on whether PsA is present, the patient's comorbidities other than PsA, previous treatment history, and the patient's drug preferences.

Efficacy and safety of sonidegib for the management of basal cell carcinoma: a drug safety evaluation.

INTRODUCTION: Surgery is the standard management for most of basal cell carcinomas (BBCs). In some cases, also radiotherapy may be a valuable weapon as well as ablative and topical treatments. However, all these approaches may be limited by some tumor features. In this scenario, locally advanced BCCs (laBCC) and metastatic BCC, also defined as 'difficult-to-treat' BCC, remain the real treatment challenge. New knowledge on BCC pathogenesis, particularly the Hedgehog (HH) pathway, led to the development of new selective therapies such as vismodegib and sonidegib. In particular, sonidegib is an orally administered small molecules, which inhibits the HH signaling pathway through the binding to SMO receptor, recently approved for the management of adult patients with laBCC who are not amenable to curative surgery or radiation therapy. AREAS COVERED: The purpose of this review is to analyze and discuss the efficacy and safety of sonidegib for the management of BCC, to provide a broad perspective on the currently available data. EXPERT OPINION: Sonidegib is a valuable weapon for the management of difficult-to-treat BCC. Current data showed promising results in terms of effectiveness and safety. However, more studies are needed to underline its role in BCC management, also considering the presence of vismodegib, and to investigate its use in a long-term period.

Clinical Characteristics of an Italian Patient Population with Advanced BCC and Real-Life Evaluation of Hedgehog Pathway Inhibitor Safety and Effectiveness.

BACKGROUND: Advanced basal cell carcinoma (aBCC) represents a complex and clinically heterogeneous group of lesions for which curative surgery and/or radiotherapy is unlikely. Systemic therapy with hedgehog pathway inhibitors (HHIs) changed the treatment landscape for this complex patient population. OBJECTIVES: The aims of the present study are to describe the clinical characteristics of a real-life Italian cohort diagnosed with aBCC and to investigate effectiveness and safety of HHI. METHODS: A multicenter observational study was performed by twelve Italian centers in the period January 1, 2016 - October 15, 2022. Patients aged ≥18 years and diagnosed with aBCC (locally advanced [laBCC] and metastatic BCC [mBCC]) were eligible for the study. Methods for investigating tumor response to HHI included clinical and dermatoscopic evaluation, radiological imaging, and histopathology. For HHI safety assessment, therapy-related adverse events (AEs) were reported and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. RESULTS: We enrolled 178 patients under treatment with HHI: 126 (70.8%) and 52 patients (29.2%) received sonidegib and vismodegib, respectively. Comprehensive data on HHI effectiveness and disease outcome were available for 132 (74.1%) of 178 patients: 129 patients had a diagnosis of laBCC (n = 84, sonidegib; n = 45, vismodegib) and 3 patients of mBCC (n = 2, vismodegib; n = 1, sonidegib, off-label). Objective response rate was 76.7% (95% confidence interval [CI]: 82.3-68.7) and 33.3% (95% CI: 88.2-1.7) for laBCC (complete response [CR]: 43/129; PR: 56/129) and mBCC (CR: 0/3; PR: 1/3), respectively. High-risk aBCC histopathological subtypes and occurrence of >2 therapy-related AEs were significantly associated with nonresponse to HHI therapy ([OR: 2.61; 95% CI: 1.09-6.05; p: 0.03] and [OR: 2.74; 95% CI: 1.03-7.9; p: 0.04]), respectively. Majority of our cohort (54.5%) developed at least 1 therapy-related AE, most of which were mild-moderate in severity. CONCLUSIONS: Our results demonstrate the effectiveness and safety profile of HHI and confirm the reproducibility of pivotal trial results in real-life clinical setting.

Management of Advanced Invasive Melanoma: New Strategies.

The incidence of cutaneous melanoma (CM) is increasing. CM is defined as melanoma in situ when limited within the epidermis and invasive when atypical melanocytes progressively invade the dermis. Treatment of CM is challenging. On one hand, melanoma in situ does not require further treatment except for a limited secondary excision with reduced margins to minimize the risk of local recurrences; on the other, invasive melanoma requires a personalized approach based on tumor staging. Consequently, an association of surgical and medical treatments is often necessary for invasive forms of the disease. In this scenario, new knowledge on melanoma pathogenesis has led to the development of safe and effective treatments, and several drugs are currently under investigation. However, extensive knowledge is required to offer patients a tailored-tail approach. The aim of our article was to review current literature to provide an overview of treatment options for invasive melanoma, highlighting strategical approaches that can be used in patients with these forms of disease.

Stardust Pattern as Evolution of Pigmented Spitz Nevi During Childhood.

INTRODUCTION: Spitz nevi (SN) are benign melanocytic proliferations frequently occurring in children. Some pigmented SN with a starburst pattern evolve into the "stardust" one, which is characterized by a central, black to gray, hyperpigmented area and remnants of a brown network at the periphery. These dermoscopy changes are often the first alert to induce excision. OBJECTIVES: The aim of this study is to enlarge the case series of stardust SN in children, in order to increase confidence with this new dermoscopic pattern and reduce unnecessary excisions. METHODS: This retrospective observational study was conducted with SN cases received from IDS members. The inclusion criteria were: clinical and/or histopathologic diagnosis of Spitz naevus with starburst appearance in children <12 years old, availability of a dermoscopic image at baseline and after follow-up of at least 1 year, availability of patient data. The dermoscopic images and their changes over time were assessed by three evaluators in consensus. RESULTS: 38 SN were enrolled, with a median age of 7 years and a median FUP duration of 15,5 months. Comparing the evolution with time of FUP, no significant differences were found between growing and involuting lesions in terms of patient age and sex, location and palpability of lesions. CONCLUSIONS: The long follow-up reported in our study could really support the concept of benignity of changing SN. A conservative approach is acceptable for nevi showing the stardust pattern, because it may be considered a physiological evolution of pigmented Spitz nevus, and urgent surgeries could be avoided.