Dermatologic toxicities to inhibitors of cyclin-dependent kinases CDK 4 and 6: An updated review for clinical practice.

Cyclin-dependent kinase (CDK) 4/6 inhibitors (palbociclib, ribociclib and abemaciclib) have revolutionized the treatment of metastatic breast carcinoma. They currently form the first-line treatment, in combination with endocrine agents, for the management of locally advanced or metastatic hormone receptor-positive (HR + ), human epidermal growth factor receptor 2-negative (HER2-) breast cancer, the largest subtype of breast carcinoma. CDK 4/6 inhibitors have shown comparable efficacy outcomes with predictable and manageable adverse events. In this setting, dermatologic toxicity appears to be relatively frequent, accounting for up to 15% of all reported adverse events. It is usually mild to moderate in intensity and does not normally constitute a dose-limiting toxicity. The range of dermatologic adverse events includes both non-specific entities (maculopapular rash, pruritus, alopecia) and more characteristic toxicities related to CDK4/6 inhibitors, such as vitiligo-like lesions or cutaneous lupus erythematosus. Finally, more severe or life-threatening skin reactions can occasionally occur. The main dermatologic manifestations associated with CDK4/6 inhibitors, as well as management thereof, are described in this comprehensive review.

Oral mucosal toxicities induced by immune checkpoint inhibitors: Clinical features and algorithm management.

Immune checkpoint inhibitors (ICIs) have emerged as standard therapies for an increasing number of advanced cancers. Nonspecific immune activation may lead to immune-related adverse events among which dermatological reactions are one of the most prevalent (all-grade incidence ranging from 30 to 60%). Oral mucosal adverse reactions to ICIs are far less common than cutaneous adverse events. However, a spectrum of oral changes with characteristic features has recently emerged, including lichenoid reactions, sicca syndrome, and even autoimmune bullous disorders with oral involvement. Oral changes mainly occur during the first year of treatment, often concurrently with other dermatological changes, and may involve up to 10% of patients under ICI therapies. This article provides a systematic review of the oral changes reported with these therapies based on a rich iconography.

Anticancer treatments and photosensitivity.

Drug-induced photosensitivity is associated with a wide range of anticancer treatments, including conventional chemotherapeutic agents, targeted anticancer therapies, and immune checkpoint inhibitors. These dermatologic adverse events can have a major impact on the well-being and quality of life of cancer patients, leading to dose modifications and interruption or discontinuation of anticancer treatments in severe cases. However, the heterogeneous nature of the photosensitive reactions induced by these agents, as well as the common concomitant use of other potentially photosensitizing drugs (antibiotics, voriconazole, nonsteroidal anti-inflammatory drugs, etc.), can make the diagnosis and, therefore the prevention, of these adverse events particularly challenging. The aim of this review is to describe the most characteristic forms of photosensitivity observed in patients being treated with anticancer treatments, including phototoxicity and photoallergy, and other potentially photo-induced manifestations such as UV recall, exaggerated sunburn reactions associated with treatment-related vitiligo, drug-induced cutaneous lupus erythematosus, and UV-induced hyperpigmentation. We also discuss the photosensitive reactions recently reported with new-generation targeted anticancer therapies and immune checkpoint inhibitors and highlight the importance of continued surveillance to identify photosensitizing agents, and of educating patients on the need for preventive UVA/UVB photoprotective measures.

French guidelines for the management of oral lichen planus (excluding pharmacological therapy).

INTRODUCTION: Oral lichen is a chronic inflammatory disease for which diagnostic management and follow-up are heterogeneous given the absence of specific guidelines in France. Our objective was to develop French multidisciplinary guidelines for the management of oral lichen. MATERIALS AND METHODS: Working groups from the Groupe d'Etude de la Muqueuse Buccale (GEMUB) formulated a list of research questions and the corresponding recommendations according to the "formal consensus" method for developing practice guidelines. These recommendations were submitted to a group of experts and the degree of agreement for each recommendation was assessed by a scoring group. RESULTS: Twenty-two research questions, divided into 3 themes (nosological classification and initial assessment, induced oral lichenoid lesions, and follow-up) resulted in 22 recommendations. Initial biopsy for histology is recommended in the absence of reticulated lesions. Biopsy for direct immunofluorescence is recommended for ulcerated, erosive, bullous types and for diffuse erythematous gingivitis. Management should include a periodontal and dental check-up, and investigation for extra-oral lesions. Hepatitis C testing is recommended only if risk factors are present. Definitions, triggering factors and the management of "induced oral lichenoid lesions" were clarified. Oral lichen must be monitored by a practitioner familiar with the disease at least once a year, using objective tools. CONCLUSION: This formalised consensus of multidisciplinary experts provides clinical practice guidelines on the management and monitoring of oral lichen.

European recommendations for management of immune checkpoint inhibitors-derived dermatologic adverse events. The EADV task force 'Dermatology for cancer patients' position statement.

The introduction of immune checkpoint inhibitors (ICIs) opened a new era in oncologic therapy. The favourable profile of ICIs in terms of efficacy and safety can be overshadowed by the development of immune-related adverse events (irAEs). Dermatologic irAEs (dirAEs) appear in about 40% of patients undergoing immunotherapy and mainly include maculopapular, psoriasiform, lichenoid and eczematous rashes, auto-immune bullous disorders, pigmentary disorders, pruritus, oral mucosal lesions, hair and nail changes, as well as a few rare and potentially life-threatening toxicities. The EADV task force Dermatology for Cancer Patients merged the clinical experience of the so-far published data, incorporated the quantitative and qualitative characteristics of each specific dirAEs, and released dermatology-derived, phenotype-specific treatment recommendations for cutaneous toxicities (including levels of evidence and grades of recommendation). The basic principle of management is that the interventions should be tailored to serve the equilibrium between patients' relief from the symptoms and signs of skin toxicity and the preservation of an unimpeded oncologic treatment.

Toxicités dermatologiques après prise en charge d'un cancer du sein : intérêt d'une cure thermale en soins oncologiques de support: Long lasting cutaneous adverse events after breast cancer and evaluation of hydrotherapy as supportive care.

Dermatological toxicities (affecting the skin, mucous membranes, nails or hair) are frequently associated with cancer treatments. They can represent a real burden for patients, with physical, social and psychological repercussions. These dermatological adverse events can also persist long after the treatment has ended, especially after treatment with cytotoxic chemotherapeutic agents such as taxanes. There is a clear need for the development of suitable supportive care measures to help manage these toxicities. The place of a hydrotherapy treatment in this context remains to be clarified. This article summarizes the main data available on the quality of life, and more specifically the dermatological quality of life, of patients for whom hydrotherapy was proposed after breast cancer. © 2020 Elsevier Masson SAS. All rights reserved.

[Immune-related adverse events after immune checkpoints inhibitors in 2019: An update]. / Toxicités immunologiques induites par les inhibiteurs de checkpoint en 2019 : mise au point.

Use of checkpoint inhibitors to treat cancer was one of the most important revolution these last years and an increasing number of new types of tumors is currently under investigation with these new treatments. However, immune-related adverse events associated with these agents frequently affect various organs, mimicking auto-immune or inflammatory diseases. Some of these effects can be severe, often requiring hospitalization and specialized treatment (immunosuppression). Most known agents are ipilimumab (anti-CTLA-4 antibody) nivolumab and pembrolizumab (anti-PD-1 antibodies). New molecules are now approved or in development as anti-PD-L1 antibodies, anti-LAG-3 or anti-TIM-3 antibodies, increasing the probability and new description of immune-related adverse events. With his experience in auto-immune diseases, the immunologist/internal medicine specialist has an important role in the management of these toxicities. The goal of this review is to focus on the incidence, diagnostic assessment and recommended management of the most relevant immune-related adverse events.

[Treatment of patients with brain metastases from a melanoma]. / Prise en charge des patients atteints de métastases cérébrales de mélanome.

Whereas immune checkpoint inhibitors of serine/threonine protein kinase B-raf therapy dramatically changed metastatic outcomes of patients with melanoma, they remain at high risk of brain extension. Additional local treatment can be offered in this situation such as surgery and or stereotactic radiotherapy. In this review article, we describe the different options with published data and their optimal timing.

[Toxicity of immune checkpoints inhibitors]. / Toxicité des inhibiteurs de points de contrôle immunitaires.

INTRODUCTION: Anti-tumoral immunotherapy is currently the basis of a profound modification of therapeutic concepts in oncology, in particular since the arrival of immune checkpoint inhibitors (ICI). In addition to their efficacy profile, these immune-targeted agents also generate adverse events. With the increasing use of ICI for a growing number of tumor types, awareness of immunotherapy-related adverse events is essential to ensure prompt diagnosis and effective management of these potentially serious adverse events. BACKGROUND: Cytotoxic T-lymphocyte antigen 4 (CTLA4) and programmed cell death protein 1 (PD1) are two co-inhibitory receptors that are expressed on activated T cells against which therapeutic blocking antibodies have reached routine clinical use. Immune checkpoint blockade can induce inflammatory adverse effects, termed immune-related adverse events (irAEs), which resemble autoimmune disease. Though severe irAEs remain rare, they can be fatal if not diagnosed and treated in an appropriate manner. OUTLOOK AND CONCLUSION: Additional studies are needed to better understand the clinical characteristics and chronology of these adverse effects and to clarify their pathophysiological mechanisms.