Anti-PD1 in Merkel cell carcinoma and cutaneous squamous cell carcinoma, description of five cases and recent data from the literature

International audienceno abstrac

Chemotherapy efficacy after first-line immunotherapy in 18 advanced melanoma patients

International audienceIn BRAF wild type advanced melanoma, immune checkpoint blockers such as anti-PD1 (anti-programmed cell death 1) are usually continued beyond progression for a hypothetical rare further response. Chemotherapy as a second-line option is considered ineffective by many practitioners based on historical data. Continuing anti-PD1 beyond progression has a high health-economic impact and is not recommended by the FDA. This study aimed to describe the efficacy and survival of advanced melanoma patients who received second-line (or more) chemotherapy after immunotherapy failure. This was a retrospective single center study conducted in a French University Hospital during an 11-month period. All advanced melanoma patients treated with chemotherapy after immunotherapy failure were included. Eighteen patients were analyzed. Therapeutic response to chemotherapy was evaluable in 16 patients: partial response was achieved in 3/16 (19%), stable disease in 1/16 (6%) and progressive disease in 12/16 (75%). Median overall survival from chemotherapy start was 12 months. Median progression-free survival was 5.4 months. The 6-month overall survival rate was 81% and the 6-month progression-free survival rate was 40%. Although the disease control rate with chemotherapy was low (25%), survival data in our study are far superior to those previously published. This could be linked to a high proportion of patients treated with anti-PD1 just prior to chemotherapy, which may suggest a potential synergy between immunotherapy and chemotherapy

Pyoderma Gangrenosum Under Dabrafenib and Trametinib for Metastatic Melanoma

International audienceno abstrac

First case of trastuzumab emtansine-associated hemorrhagic telangiectasias treated with propranolol

International audienceno abstrac

Positive margins after surgical excision of locoregional cutaneous melanoma metastasis and their impact on patient outcome

International audienceFor melanoma patients, surgery is a standard treatment for locoregional skin metastasis (LSM). To assess the frequency and risk factors for positive margins after excision of LSM and their impact on patient overall survival (OS) and progression-free survival (PFS). A monocentric, retrospective observational study was performed including 87 patients with LSM who had undergone surgical excision. Positive margins were found in 45% of patients after excision. After additional excision, 28% of patients still had positive margins. Interestingly, there was no difference in PFS or OS for clear margins after the first or additional excision or for margins that remained positive without additional excision. LSM size was the only identified predictive factor for positive margins. This is the first reported study investigating the frequency of, and risk factors for positive margins of cutaneous LSM, which raises the question of whether additional excision should be performed following positive margin excision

Are checkpoint inhibitors a valuable option for metastatic or unresectable vulvar and vaginal melanomas?

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Profile of vemurafenib-induced severe skin toxicities

International audienceBACKGROUND: Vemurafenib, a BRAF inhibitor, is commonly associated with skin toxicity. The impact of severe forms is unknown.OBJECTIVE: To determine the rate of permanent vemurafenib discontinuation due to grade 3-4 skin toxicity, features of these toxicities, their recurrence rate after a switch to dabrafenib and their impact on overall survival.METHODS: Retrospective cohort study of 131 patients treated with vemurafenib for melanoma between November 2010 and December 2014. Data on skin toxicities, the need for vemurafenib adjustment and the impact of switching to dabrafenib were collected. Regarding survival analysis, a conditional landmark analysis was performed to correct lead-time bias.RESULTS: Among the 131 vemurafenib-treated patients, 26% developed grade 3-4 skin toxicity. Forty-four percent of them permanently discontinued their treatment, mainly due to rash and classic skin adverse reactions (Steven-Johnson syndrome, Drug Reaction with Eosinophilia and Systemic Symptoms). Conversely, photosensitivity and carcinomas rarely required treatment adjustment. Grade 3-4 rashes were associated with clinical or biological abnormalities in 94% of patients. Among the 10 patients who subsequently switched to dabrafenib, skin toxicity recurred only in one patient. Overall survival was significantly prolonged in case of severe skin toxicity emerging within the first 4 (P = 0.014) and 8 weeks (P = 0.038) on vemurafenib, with only a trend at 12 weeks (P = 0.052). Median overall survival was also prolonged in case of severe rash.CONCLUSION: In this study, vemurafenib was continued in 56% of patients with grade 3-4 skin toxicity, which was associated with prolonged overall survival when emerging within the first 4 and 8 weeks of treatment. While developing severe skin adverse reactions permanently contraindicates vemurafenib use, other rashes should lead to retreatment attempts with dose reduction. In case of recurrence, dabrafenib seems to be an interesting option. For other skin toxicities, including photosensitivity and cutaneous carcinoma, treatment adjustment is usually not needed

Vorinostat for Refractory or Relapsing Epidermotropic T-cell Lymphoma: A Retrospective Cohort Study of 15 Patients

International audienceSince the approval of vorinostat for the treatment of refractory cutaneous epidermotropic T-cell lymphoma (CTCL) in 2006, very little data about this treatment have been published. The aim of this retrospective study was to assess the efficacy and safety of vorinostat in patients with CTCL treated between 2007 and 2013 in our department. Fifteen patients (median age 64 years) were included: 9 with Sézary syndrome and 6 with mycosis fungoides. They were all in progression and the median number of systemic treatments previously administered was 3 (range 1-7). With vorinostat treatment, the best response was partial remission in 5 patients (33%) and stabilization in 4 patients (27%). Six patients experienced disease progression. The mean time to response and response duration were 70 (range 31-140) and 300 days (range 157-663) , respectively. The most frequent adverse events were asthenia, weight loss, nausea and anaemia. Vorinostat could be a therapeutic alternative for CTCL after treatment failure

Blood Predictive Biomarkers for Nivolumab in Advanced Melanoma

Nivolumab response rate is 40% in metastatic melanoma. Few studies have evaluated pre-treatment biomarkers predictive of response. The aim of this study was to identify potential peripheral blood biomarkers associated with survival in patients with advanced melanoma treated with nivolumab. All advanced melanoma cases treated with anti-programmed cell death protein 1 (anti-PD1) over a 3-year period in the Dermato-Oncology Department, Nantes, France were identified. For each case, 9 potential blood biomarkers were identified. Bivariate and multivariate analyses, adjusted for the American Joint Committee on Cancer (AJCC) classification stage, Eastern Cooperative Oncology Group (ECOG) performance status, lactate dehydrogenase (LDH) level and failure to respond to first-line therapy, were used to test the association between biomarkers and overall survival (primary outcome) or progression-free survival (secondary outcome). Increased monocyte count, leukocyte/lymphocyte ratio and neutrophil/lymphocyte ratio were significantly associated with decreased overall survival after bivariate and multivariate analyses. Increased monocyte count was also significantly associated with decreased progression-free survival. These blood variables are easily measured and could help to predict patient response before the introduction of anti-PD1 therapy