Background An improvement in overall survival among patients with metastatic melanoma has been an elusive goal. In this phase 3 study, ipilimumab — which blocks cytotoxic T-lymphocyte–associated antigen 4 to potentiate an antitumor T-cell response — administered with or without a glycoprotein 100 (gp100) peptide vaccine was compared with gp100 alone in patients with previously treated metastatic melanoma. Methods A total of 676 HLA-A*0201–positive patients with unresectable stage III or IV melanoma, whose disease had progressed while they were receiving therapy for metastatic disease, were randomly assigned, in a 3:1:1 ratio, to receive ipilimumab plus gp100 (403 patients), ipilimumab alone (137), or gp100 alone (136). Ipilimumab, at a dose of 3 mg per kilogram of body weight, was administered with or without gp100 every 3 weeks for up to four treatments (induction). Eligible patients could receive reinduction therapy. The primary end point was overall survival. Results The median overall survival was 10.0 months among patients receiving ipilimumab plus gp100, as compared with 6.4 months among patients receiving gp100 alone (hazard ratio for death, 0.68; P<0.001). The median overall survival with ipilimumab alone was 10.1 months (hazard ratio for death in the comparison with gp100 alone, 0.66; P = 0.003). No difference in overall survival was detected between the ipilimumab groups (hazard ratio with ipilimumab plus gp100, 1.04; P = 0.76). Grade 3 or 4 immune-related adverse events occurred in 10 to 15% of patients treated with ipilimumab and in 3% treated with gp100 alone. There were 14 deaths related to the study drugs (2.1%), and 7 were associated with immune-related adverse events. Conclusions Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma. Adverse events can be severe, long-lasting, or both, but most are reversible with appropriate treatment. (Funded by Medarex and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00094653.)

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Improved Survival with Ipilimumab in Patients with Metastatic Melanoma.

Background Blockade of programmed death 1 (PD-1), an inhibitory receptor expressed by T cells, can overcome immune resistance. We assessed the antitumor activity and safety of BMS-936558, an antibody that specifically blocks PD-1. Methods We enrolled patients with advanced melanoma, non–small-cell lung cancer, castrationresistant prostate cancer, or renal-cell or colorectal cancer to receive anti–PD-1 antibody at a dose of 0.1 to 10.0 mg per kilogram of body weight every 2 weeks. Response was assessed after each 8-week treatment cycle. Patients received up to 12 cycles until disease progression or a complete response occurred. Results A total of 296 patients received treatment through February 24, 2012. Grade 3 or 4 drugrelated adverse events occurred in 14% of patients; there were three deaths from pulmonary toxicity. No maximum tolerated dose was defined. Adverse events consistent with immune-related causes were observed. Among 236 patients in whom response could be evaluated, objective responses (complete or partial responses) were observed in those with non–small-cell lung cancer, melanoma, or renal-cell cancer. Cumulative response rates (all doses) were 18% among patients with non–small-cell lung cancer (14 of 76 patients), 28% among patients with melanoma (26 of 94 patients), and 27% among patients with renal-cell cancer (9 of 33 patients). Responses were durable; 20 of 31 responses lasted 1 year or more in patients with 1 year or more of follow-up. To assess the role of intratumoral PD-1 ligand (PD-L1) expression in the modulation of the PD-1–PD-L1 pathway, immunohistochemical analysis was performed on pretreatment tumor specimens obtained from 42 patients. Of 17 patients with PD-L1–negative tumors, none had an objective response; 9 of 25 patients (36%) with PD-L1–positive tumors had an objective response (P = 0.006). Conclusions Anti–PD-1 antibody produced objective responses in approximately one in four to one in five patients with non–small-cell lung cancer, melanoma, or renal-cell cancer; the adverse-event profile does not appear to preclude its use. Preliminary data suggest a relationship between PD-L1 expression on tumor cells and objective response. (Funded by Bristol-Myers Squibb and others; ClinicalTrials.gov number, NCT00730639.)

https://www.nejm.org/doi/pdf/10.1056/NEJMoa1200690

Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.

Background: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Association's (ATA's) guidelines for the management of these disorders were revised in 2009, significant scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid nodules and differentiated thyroid cancer. Methods: The specific clinical questions addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of task force members. Task force panel members were educated on knowledge synthesis methods, including electronic database searching, review and selection of relevant citations, and critical appraisal of selected studies. Published English language articles on adults were eligible for inclusion. The American College of Physicians Guideline Gr...

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2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer.

BackgroundPembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non–small-cell lung cancer (NSCLC), with increased activity in tumors that express programmed death ligand 1 (PD-L1). MethodsIn this open-label, phase 3 trial, we randomly assigned 305 patients who had previously untreated advanced NSCLC with PD-L1 expression on at least 50% of tumor cells and no sensitizing mutation of the epidermal growth factor receptor gene or translocation of the anaplastic lymphoma kinase gene to receive either pembrolizumab (at a fixed dose of 200 mg every 3 weeks) or the investigator’s choice of platinum-based chemotherapy. Crossover from the chemotherapy group to the pembrolizumab group was permitted in the event of disease progression. The primary end point, progression-free survival, was assessed by means of blinded, independent, central radiologic review. Secondary end points were overall survival, objective response rate, and safety. ResultsMedi...

https://www.nejm.org/doi/suppl/10.1056/NEJMoa1606774/suppl_file/nejmoa1606774_protocol.pdf

Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer

At 6 months, overall survival was 84% (95% confidence interval [CI], 78 to 89) in the vemurafenib group and 64% (95% CI, 56 to 73) in the dacarbazine group. In the interim analysis for overall survival and final analysis for progression-free survival, vemurafenib was associated with a relative reduction of 63% in the risk of death and of 74% in the risk of either death or disease progression, as compared with dacarbazine (P<0.001 for both comparisons). After review of the interim analysis by an independent data and safety monitoring board, crossover from dacarbazine to vemurafenib was recommended. Response rates were 48% for vemurafenib and 5% for dacarbazine. Common adverse events associated with vemurafenib were arthralgia, rash, fatigue, alopecia, keratoacanthoma or squamous-cell carcinoma, photosensitivity, nausea, and diarrhea; 38% of patients required dose modification because of toxic effects. Conclusions Vemurafenib produced improved rates of overall and progression-free survival in patients with previously untreated melanoma with the BRAF V600E mutation. (Funded by Hoffmann–La Roche; BRIM-3 ClinicalTrials.gov number, NCT01006980.)

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Improved Survival with Vemurafenib in Melanoma with BRAF V600E Mutation

IntroductionLa TEP-TDM au FDG a des indications bien validees pour certaines pathologies tumorales, cancer pulmonaire et lymphomes notamment. Les indications de la TEP-TDM au FDG pour le bilan de melanome cutane sont moins claires.MethodesApres un rappel sur les caracteristiques des produits et des machines utilisees en TEP-TDM, nous avons utilise les SOR et les derniers articles scientifiques pour determiner quels patients peuvent attendre un benefice de cet examen.ResultatsLa TEP-TDM n’est pas indiquee pour le diagnostic de malignite d’une lesion cutanee suspecte ni pour la recherche de metastases ganglionnaires locoregionales. La TEP-TDM n’est pas indiquee pour le bilan d’extension initial des melanomes sans atteinte ganglionnaire. La TEP-TDM pourrait etre proposee en cas de melanome epais et de macrometastase du ganglion sentinelle (GS) associee. La TEP-TDM permet le bilan d’extension a distance. Le seul traitement curateur du melanome etant actuellement le traitement chirurgical, les indications privilegiees de la TEP-TDM sont le bilan d’extirpabilite d’une (ou plusieurs) metastase(s) ganglionnaire(s) ou viscerale(s), que ces metastases soient suspectees ou confirmees histologiquement. La TEP-TDM, faite en preoperatoire, permet d’eviter une chirurgie inutile chez un patient deja polymetastatique. La TEP-TDM n’est pas indiquee pour completer le bilan d’extension d’un patient polymetastatique connu. La TEP-TDM n’est pas indiquee pour l’evaluation de la reponse a la chimiotherapie, hors protocoles de recherche clinique.

Place de la TEP-TDM au FDG dans le mélanome cutané

e20040Background: Advanced stage cutaneous T-cell lymphomas (CTCLs) remain an unmet medical need. Immunomodulatory agents such as mogamulizumab, anti-KIR3DL2 and brentuximab vedotin (BV), an anti-C...

Effect of expression of ICOS in cutaneous T-cell lymphoma and its targeting on killing of malignant cells.

[Winkelmann-Muller generalized eruptive histiocytoma. Ultrastructural and immunohistochemical study].

2005 was also the inaugural joining together of EDEN and the European Society of Dermatology Research (ESDR). This successful collaboration involved epidemiology plenary sessions and a scientifi c symposium being held alongside the ESDR main meeting. EDEN will maintain an active alliance with the ESDR annual meetings. The EDEN group has recently published a systematic review of interventions for hand eczema [1] . This review is in the fi nal stages of preparation for publication as a Cochrane systematic review. A further major piece of work was the compilation of a database of randomised controlled trials of interventions for psoriasis which is currently being updated [2] . The group are also actively involved in recording randomised controlled trials in atopic eczema. All of these databases are being actively maintained with a view to the establishment of a world collection of literature in this fi elds which will be regularly updated and accessible on the EDEN website for future research. A new research project is being developed to look at the prevalence of common skin diseases and fragrance allergy in Europe. There is also a strong focus on the development of trans-cultural instruments for use in future studies with closer links across European countries. An EDEN project on quality of life (QOL) is currently under evaluation by members. The European Dermato-Epidemiology Network (EDEN) is an active group of researchers in the fi eld of dermato-epidemiology. The aims of the group are to expand the role of epidemiology in dermatology, to share expertise and to produce high-quality multi-centre collaborative work. EDEN is involved in the dissemination of information, teaching, training and organising working groups to address important research questions about the distribution, causes and treatment of skin disease. EDEN holds triennial congresses, the most recent being in Venice in October 2004. This meeting was held in conjunction with the International Dermatoepidemiology Association, an umbrella organisation that includes other dermato-epidemiology groups worldwide. This meeting was the forum for presentation of new research from worldwide centres involved in dermato-epidemiology research. The group also co-ordinates annual workshops; in 2005 the title of the workshop was ‘Sunscreens, photo-protection and public health’. This was a 2-day workshop of active discussion and debate with invited world leaders in the fi eld addressing the controversies and research agenda needed in this fi eld. Future workshops are being planned to focus on confl ict of Interest, skin cancer and other ‘hot topics’ in dermato-epidemiology.

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Jean-Jacques Grob

Papers

Place de la TEP-TDM au FDG dans le mélanome cutané

Effect of expression of ICOS in cutaneous T-cell lymphoma and its targeting on killing of malignant cells.

[Winkelmann-Muller generalized eruptive histiocytoma. Ultrastructural and immunohistochemical study].

Update on the activities of the European Dermato-Epidemiology Network (EDEN).

Is there any interest in a new BRAF-MEK inhibitor combination in melanoma?