B Dreno

Centre Hospitalier Universitaire de Nantes, Naoned, Pays de la Loire, France

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Publications (539)2003.7 Total impact

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    ABSTRACT: The Hedgehog pathway inhibitor vismodegib has shown clinical benefit in patients with advanced basal cell carcinoma and is approved for treatment of patients with advanced basal cell carcinoma for whom surgery is inappropriate. STEVIE was designed to assess the safety of vismodegib in a situation similar to routine practice, with a long follow-up. In this multicentre, open-label trial, adult patients with histologically confirmed locally advanced basal cell carcinoma or metastatic basal cell carcinoma were recruited from regional referral centres or specialist clinics. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, and adequate organ function. Patients with locally advanced basal cell carcinoma had to have been deemed ineligible for surgery. All patients received 150 mg oral vismodegib capsules once a day on a continuous basis in 28-day cycles. The primary objective was safety (incidence of adverse events until disease progression or unacceptable toxic effects), with assessments on day 1 of each treatment cycle (28 days) by principal investigator and coinvestigators at the site. Efficacy variables were assessed as secondary endpoints. The safety evaluable population included all patients who received at least one dose of study drug. Patients with histologically confirmed basal cell carcinoma who received at least one dose of study drug were included in the efficacy analysis. An interim analysis was pre-planned after 500 patients achieved 1 year of follow-up. This trial is registered with ClinicalTrials.gov, number NCT01367665. The study is still ongoing. Between June 30, 2011, and Nov 6, 2014, we enrolled 1227 patients. At clinical cutoff (Nov 6, 2013), 499 patients (468 with locally advanced basal cell carcinoma and 31 with metastatic basal cell carcinoma) had received study drug and had the potential to be followed up for 12 months or longer. Treatment was discontinued in 400 (80%) patients; 180 (36%) had adverse events, 70 (14%) had progressive disease, and 51 (10%) requested to stop treatment. Median duration of vismodegib exposure was 36·4 weeks (IQR 17·7-62·0). Adverse events happened in 491 (98%) patients; the most common were muscle spasms (317 [64%]), alopecia (307 [62%]), dysgeusia (269 [54%]), weight loss (162 [33%]), asthenia (141 [28%]), decreased appetite (126 [25%]), ageusia (112 [22%]), diarrhoea (83 [17%]), nausea (80 [16%]), and fatigue (80 [16%]). Most adverse events were grade 1 or 2. We recorded serious adverse events in 108 (22%) of 499 patients. Of the 31 patients who died, 21 were the result of adverse events. As assessed by investigators, 302 (66·7%, 62·1-71·0) of 453 patients with locally advanced basal cell carcinoma had an overall response (153 complete responses and 149 partial responses); 11 (37·9%; 20·7-57·7) of 29 patients with metastatic basal cell carcinoma had an overall response (two complete responses, nine partial responses). This study assessed the use of vismodegib in a setting representative of routine clinical practice for patients with advanced basal cell carcinoma. Our results show that treatment with vismodegib adds a novel therapeutic modality from which patients with advanced basal cell carcinoma can benefit substantially. F Hoffmann-La Roche. Copyright © 2015 Elsevier Ltd. All rights reserved.
    The Lancet Oncology 05/2015; DOI:10.1016/S1470-2045(15)70198-1 · 24.73 Impact Factor
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    ABSTRACT: Tumor immune escape has recently been shown to be related to the development of an immune tolerance state of the microenvironment. Cytokines activating the immune system such as IFN-γ can be used to reverse the immune escape and thus to potentiate the efficacy of immunotherapy. A clinical study was conducted in 18 stage IIIc/IV melanoma patients treated with tumor-infiltrating lymphocytes (TILs) in combination with intratumoral TG1042 injection (adenovirus expressing IFN-γ). The primary objective was to investigate the safety of treatment. Secondary objectives were to study the clinical response and translational research. The treatment was well tolerated. Among the 13 patients evaluable for tumor response, 38.5 % had an overall objective response (OOR = CR + PR) and disease control rate (DCR = CR + PR + S) of 46 %. The clinical response of the 37 targeted lesions led to an OOR of 51 % and a DCR of 75 %. Translational research on predictive markers did not significantly differ between responder and non-responder patients. However, specifically regarding injected lesions, the clinical response correlated with CD3-/CD56+ NK cells which could be activated by TG1042. Further larger studies of this combined immunotherapy are needed to confirm our findings. Intralesional TG1042 combined with antigen-selected TILs should be discussed.
    Cancer Immunology and Immunotherapy 04/2015; DOI:10.1007/s00262-015-1691-7 · 3.94 Impact Factor
  • A.-C. Knol, B. Dréno
    03/2015; 49(1). DOI:10.1016/S1761-2896(15)70046-4
  • Annales de Dermatologie et de Vénéréologie 03/2015; DOI:10.1016/j.annder.2014.12.005 · 0.67 Impact Factor
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    ABSTRACT: Acne vulgaris (acne) is a chronic inflammatory disease of the sebaceous gland, characterized by follicular hyperkeratinization, excessive colonization by Propionibacterium acnes (P. acnes) as well as immune reactions and inflammation. Despite an armamentarium of topical treatments available including benzoyl peroxide, retinoids and azelaic acid, topical antibiotics in monotherapies, especially erythromycin and clindamycin, are still used in Europe to treat acne. This intensive use led to antimicrobial-resistant P. acnes and staphylococci strains becoming one of the main health issues worldwide. This is an update on the current topical acne treatments available in Europe, their mechanism of action, their potential to induce antimicrobial resistance and their clinical efficacy and safety. © 2015 European Academy of Dermatology and Venereology.
    Journal of the European Academy of Dermatology and Venereology 02/2015; DOI:10.1111/jdv.12989 · 3.11 Impact Factor
  • 01/2015; 1(1):27-29. DOI:10.1016/j.jdcr.2014.10.005
  • Annales de Dermatologie et de Vénéréologie 12/2014; 141(s 6–7):S85. DOI:10.1016/j.annder.2014.09.039 · 0.67 Impact Factor
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    ABSTRACT: Extensive rhinectomy or full-thickness defects are not uncommon, in particular in the treatment of skin cancer. The present study lays out the principles of choice and creation of prostheses for nasal reconstruction. Prosthetic nasal reconstruction in France depends on a specialist prescription drawn up under the “Ocular and Facial Prostheses” rubric of the official List of Products and Procedures. National health insurance cover is 100% on condition that the prosthesis is produced by an approved prosthetist. The present study describes production stages, forms and means of fixation, and the timeline of implantation. Nasal prosthetic repair is simple, fast and functional, allowing social rehabilitation despite full respect of carcinologic margins, and without ruling out subsequent multilayer reconstruction. Benefits and drawbacks, and the factors determining repair options according to pathologic context are discussed. Nasal prostheses are an integral option in the repair of full-thickness nasal defects and total rhinectomies. The head and neck surgeon needs expertise in indications and techniques of reconstruction, so as to prescribe nasal prostheses as the context demands.
    European Annals of Otorhinolaryngology, Head and Neck Diseases 12/2014; 132(2). DOI:10.1016/j.anorl.2014.02.007
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    ABSTRACT: Background Verneuil's disease is a chronic inflammatory skin disease of the follicles in apocrine glands rich area of the skin (axillary, inguinal, anogenital) and is associated with a deficient skin innate immunity. It is characterized by the occurrence of nodules, abscesses, fistulas, scars. Recently, vitamin D has been shown to stimulate skin innate immunity.Objective The primary objective of the study was to assess whether Verneuil's disease was associated with vitamin D deficiency. The secondary objective was to determine whether vitamin D supplementation could improve inflammatory lesions.Methods First, 25(OH) vitamin D3 serum levels in patients with Verneuil's disease followed at Nantes University Hospital were compared to those of healthy donors from the French Blood Bank. Then, a pilot study was conducted in 14 patients supplemented with vitamin D according to their vitamin D level at baseline at months 3 and 6. The endpoints at 6 months were decreased by at least 20% in the number of nodules and in the frequency of flare-ups.ResultsTwenty-two patients (100%) had vitamin D deficiency (level <30 ng/mL) of whom 36% were severely deficient (level <10 ng/mL), having correlation with the disease severity (P = 0.03268) vs. 20 controls with vitamin D deficiency (91%) of whom 14% were severely deficient. In 14 patients, the supplementation significantly decreased the number of nodules at 6 months (P = 0.01133), and the endpoints were achieved in 79% of these patients. A correlation between the therapeutic success and the importance of the increase in vitamin D level after supplementation was observed (P = 0.01099).Conclusion Our study shows that Verneuil's disease is associated with a major vitamin D deficiency, correlated with the disease severity. It suggests that vitamin D could significantly improve the inflammatory nodules, probably by stimulating the skin innate immunity. A larger randomized study is needed to confirm these findings.
    Journal of the European Academy of Dermatology and Venereology 12/2014; DOI:10.1111/jdv.12857 · 3.11 Impact Factor
  • Annales de Dermatologie et de Vénéréologie 11/2014; DOI:10.1016/j.annder.2014.09.048 · 0.67 Impact Factor
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    ABSTRACT: In the last decade, advances in molecular biology have provided evidence of the genotypic heterogeneity of melanoma. We analyzed BRAF, NRAS and c-KIT alterations in tissue samples from 63 stage III/IV melanoma patients and autologous cell-lines, using either allele-specific or quantitative PCR. The expression of BRAF V600E protein was also investigated using an anti-BRAF antibody in the same tissue samples. 81% of FFPE samples and tumor cell-lines harbored a genetic alteration in either BRAF (54%) or NRAS (27%) oncogenes. There was a strong concordance (100%) between tissue samples and tumor cell-lines. The BRAF V600E mutant-specific antibody showed high sensitivity (96%) and specificity (100%) for detecting the presence of a BRAF V600E mutation. The correlation was of 98% between PCR and immunohistochemistry results for BRAF mutation. These results suggest that BRAF and NRAS mutation status of tumor cells is not affected by culture conditions.This article is protected by copyright. All rights reserved.
    Experimental Dermatology 11/2014; 24(1). DOI:10.1111/exd.12584 · 4.12 Impact Factor
  • Journal of the European Academy of Dermatology and Venereology 11/2014; DOI:10.1111/jdv.12852 · 3.11 Impact Factor
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    ABSTRACT: Background Acne vulgaris is increasingly recognized in adult women; however, few studies have formally evaluated the clinical presentation and factors associated with acne in this population.Methods This prospective, observational international study evaluated the clinical characteristics and lifestyle correlates of acne in adults (≥25 years) at a dermatology visit for acne. Investigators conducted a detailed clinical examination and administered a validated questionnaire that covered medical history, disease evolution, lifestyle habits, previous treatments, skin care and quality of life.ResultsIn this study (n = 374), acne was mild or clear/almost clear in 47.3% of subjects; however, the study visit was not required to be an initial consultation for acne and as such, many patients were already on treatment. Most women (89.8%) had acne involving multiple facial zones (cheeks, forehead, mandibular area, temples) with a spectrum of facial acne severity similar to adolescents. Mixed facial acne (both inflammatory and non-inflammatory lesions present) was the most common presentation; 6.4% of women had inflammatory acne only (no non-inflammatory lesions reported) and 17.1% had comedonal acne with no inflammatory lesions. Truncal acne was present in 48.4% of patients. A small subset (11.2%) had acne localized only to the mandibular area. Compared to the women without localized acne, those with mandibular acne were more likely to be employed (90.5% vs. 78.6%), reported greater daily stress levels (5.8 vs. 5.1), and were more likely to say their jobs were psychologically stressful (71.4% vs. 57.5%). Women with mandibular acne alone were significantly less likely to have a global acne severity rating of moderate or higher (7.1% vs. 50.1%), truncal acne (19.0% vs. 51.9%), post-inflammatory hyperpigmentation (23.8% vs. 51.9%) and erythema (19.0% vs. 48.4%). At the completion of the study visit, this group was also more likely to receive a prescription for an anti-androgen (16.7% vs. 7.7%).Conclusions This study represents the first objective assessment of the facial distribution of acne lesions in adult women presenting to the dermatology office. The data surprisingly indicate that the acne distribution in almost 90% of cases is similar to that seen in adolescent acne. The stereotype of adult female acne being due to hormonal disturbances presenting as inflammatory acne localized only to the mandibular area was not found in the majority of this large group. The large majority (93.7%) of women had facial comedones. We recommend that the general treatment approach for adult acne should include agents that target each of the acne lesion subtypes. Subgroup analyses of recent large-scale controlled clinical trials have shown that many adult women respond well to standard first-line acne therapy.
    Journal of the European Academy of Dermatology and Venereology 10/2014; DOI:10.1111/jdv.12757 · 3.11 Impact Factor
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    ABSTRACT: BACKGROUND The combined inhibition of BRAF and MEK is hypothesized to improve clinical outcomes in patients with melanoma by preventing or delaying the onset of resistance observed with BRAF inhibitors alone. This randomized phase 3 study evaluated the combination of the BRAF inhibitor vemurafenib and the MEK inhibitor cobimetinib. METHODS We randomly assigned 495 patients with previously untreated unresectable locally advanced or metastatic BRAF V600 mutation-positive melanoma to receive vemurafenib and cobimetinib (combination group) or vemurafenib and placebo (control group). The primary end point was investigator-assessed progression-free survival. RESULTS The median progression-free survival was 9.9 months in the combination group and 6.2 months in the control group (hazard ratio for death or disease progression, 0.51; 95% confidence interval [CI], 0.39 to 0.68; P<0.001). The rate of complete or partial response in the combination group was 68%, as compared with 45% in the control group (P<0.001), including rates of complete response of 10% in the combination group and 4% in the control group. Progression-free survival as assessed by independent review was similar to investigator-assessed progression-free survival. Interim analyses of overall survival showed 9-month survival rates of 81% (95% CI, 75 to 87) in the combination group and 73% (95% CI, 65 to 80) in the control group. Vemurafenib and cobimetinib was associated with a nonsignificantly higher incidence of adverse events of grade 3 or higher, as compared with vemurafenib and placebo (65% vs. 59%), and there was no significant difference in the rate of study-drug discontinuation. The number of secondary cutaneous cancers decreased with the combination therapy. CONCLUSIONS The addition of cobimetinib to vemurafenib was associated with a significant improvement in progression-free survival among patients with BRAF V600-mutated metastatic melanoma, at the cost of some increase in toxicity.
    New England Journal of Medicine 09/2014; 371(20). DOI:10.1056/NEJMoa1408868 · 54.42 Impact Factor
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    ABSTRACT: Merkel cell carcinoma (MCC) is a rare and aggressive type of skin cancer that is predominantly caused by infection by the Merkel cell polyomavirus. The cell of origin for MCC is still debated because conflicting data suggest that MCC cells could be derived from Merkel cells (MCs) [1] or their precursors [2]. aggressive carcinoma characteristically occurs on sun-exposed areas of elderly white and immunosupressed patients, with approximately 50% of all tumors occuring on the face and neck and 40% in the extremities [3].This article is protected by copyright. All rights reserved.
    Experimental Dermatology 09/2014; 23(12). DOI:10.1111/exd.12546 · 4.12 Impact Factor
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    ABSTRACT: Background: Early diagnosis of melanoma can save lives. However, mass screening is not recommended, and few studies have addressed targeted screening. Objective: To evaluate a targeted melanoma screening intervention by measuring the cumulative melanoma incidence and patient compliance with the screening. Methods: This was a prospective one-year follow-up of a cohort of 3923 French patients at elevated risk of melanoma who were recruited from April to October 2011 by 78 GPs using the Self-assessment of melanoma risk score. Following standard practice, based on the GPs’ opinions, a subset of these patients was referred to dermatologists. The dermatologists scheduled excisions when required. Melanomas were confirmed using pathology reports. Patient compliance with the clinical pathway was assessed retrospectively. The cohort was followed prospectively using three data sources (GPs, dermatologists and patients). Analyses of factors associated with compliance were performed using multiple logistic regression. Results: GPs examined the skin of 3923 high-risk patients, 1506 of whom were referred to dermatologists. Nine cases of melanoma were diagnosed, corresponding to a cumulative incidence of 229.4/100 000. Of the referred patients, 57.9% attended the dermatologist consultation. Patient attendance was better when the GPs provided a dermatologist's name (OR = 2.15, 95% CI: 1.51–3.09). A delay before consulting a dermatologist was inversely associated with the estimated lesion malignancy. Conclusion: Performing this targeted screening in a high-risk population resulted in a high melanoma detection rate, despite moderate compliance. Observations suggest that naming a dermatologist is a simple, inexpensive means of increasing patient compliance with the screening.
    The European Journal of General Practice 08/2014; DOI:10.3109/13814788.2014.949669 · 0.81 Impact Factor
  • Lucie Peuvrel, Brigitte Dréno
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    ABSTRACT: Targeted therapies have developed rapidly over the last few years in the field of oncology thanks to a better understanding of carcinogenesis. They target pathways involved in signal transduction (EGFR, HER2, HER3, HER4, FLT3, RAS, RAF, MEK, KIT, RET, mTOR, SRC, EPH, SCF), tumor angiogenesis (VEGFR, TIE2), and tumor microenvironment (PDGFR, FGFR). They rarely cause the systemic adverse reactions generally associated with chemotherapy, but frequently cause disabling and specific skin toxicity. The impact on patient quality of life can be important both in terms of symptoms caused and of potentially aesthetic consequences. Inappropriate management can increase the risk of dose reduction or discontinuation of the cancer treatment. In this review, we will discuss skin toxicity associated with the main drug classes-EGFR, BRAF, MEK, mTOR, c-KIT, CTLA4, and SMO inhibitors, and anti-angiogenic agents. Targeted therapy-induced skin toxicities will be detailed in terms of symptoms, frequency, evolution, complications, and topical and oral treatments in order to improve their diagnosis and management.
    American Journal of Clinical Dermatology 08/2014; 15(5). DOI:10.1007/s40257-014-0088-2 · 2.52 Impact Factor
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    ABSTRACT: Vemurafenib is indicated for the treatment of patients with BRAF (V600) -mutant metastatic melanoma. We studied for the first time the characteristics of brain metastases developed during treatment with vemurafenib in real-life conditions. We included all patients treated over 3 years with vemurafenib in our department for metastatic melanoma without initial brain involvement. Our primary endpoint was to assess the incidence of brain metastases in these patients. Our secondary endpoints were to identify the risk factors for metastases occurrence and their characteristics and course. In our retrospective cohort of 86 patients, 20 % had developed brain metastases on average 5.3 months after vemurafenib initiation. The median follow-up was 9 months (1-26 months). Radiological examinations revealed multiple brain metastases in 41 % of patients. The only risk factor for metastasis occurrence identified was a high number of metastatic sites when initiating vemurafenib (p = 0.045). Metastasis development was associated with a trend toward a decrease in overall survival from 12.8 to 8.5 months (p = 0.07) and a significant decrease in progression-free survival from 7 to 5 months (p = 0.04). Among the patients who developed brain metastases, 82 % died, of whom 64 % within 3 months, versus 58 % of patients without brain metastases over the same period. The extra-cerebral disease was well controlled in 59 % of patients during brain progression. In vemurafenib-treated melanoma patients, brain metastases are frequent and associated with a particularly poor prognosis. Because of their high frequency in patients with controlled extra-cerebral disease, brain explorations should be systematically performed during treatment.
    Journal of Neuro-Oncology 08/2014; 120(1). DOI:10.1007/s11060-014-1533-z · 2.79 Impact Factor

Publication Stats

10k Citations
2,003.70 Total Impact Points

Institutions

  • 1990–2015
    • Centre Hospitalier Universitaire de Nantes
      • • Service de dermatologie
      • • Service de génétique médicale
      Naoned, Pays de la Loire, France
  • 1995–2014
    • University of Nantes
      Naoned, Pays de la Loire, France
  • 2013
    • University of Lille Nord de France
      Lille, Nord-Pas-de-Calais, France
  • 2009–2013
    • Hôtel-Dieu de Paris – Hôpitaux universitaires Paris Centre
      Lutetia Parisorum, Île-de-France, France
    • Cancer Research Center of Lyon
      Lyons, Rhône-Alpes, France
  • 2002–2013
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 1986–2012
    • French Institute of Health and Medical Research
      • • Epidemiology and Biostatistics Center
      • • Unit of Immunology, Dermatology, Oncology
      Lutetia Parisorum, Île-de-France, France
  • 2010
    • New York Presbyterian Hospital
      • Department of Dermatology
      New York, New York, United States
  • 1997–2010
    • Hotel Dieu Hospital
      Kingston, Ontario, Canada
  • 2007
    • Université Paris-Est Créteil Val de Marne - Université Paris 12
      Créteil, Île-de-France, France
  • 2004–2007
    • CHU de Lyon - Groupement Hospitalier Edouard Herriot
      Lyons, Rhône-Alpes, France
  • 2005
    • Société Française de Cardiologie
      Lutetia Parisorum, Île-de-France, France
  • 2001
    • Hôpital Paris Saint Joseph
      Lutetia Parisorum, Île-de-France, France
  • 1999
    • Polytech Clermont-Ferrand
      Aubière, Auvergne, France
  • 1987
    • Institut National de la Transfusion Sanguine, Paris
      Lutetia Parisorum, Île-de-France, France