F. Grange

Hôpital Universitaire Robert Debré, Lutetia Parisorum, Île-de-France, France

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Publications (191)543.1 Total impact

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    ABSTRACT: Background: In the COMBI-v trial, patients with previously untreated BRAF Val600Glu or Val600Lys mutant unresectable or metastatic melanoma who were treated with the combination of dabrafenib and trametinib had significantly longer overall and progression-free survival than those treated with vemurafenib alone. Here, we present the effects of treatments on health-related quality of life (HRQoL), an exploratory endpoint in the COMBI-v study. Methods: COMBI-v was an open-label, randomised phase 3 study in which 704 patients with metastatic melanoma with a BRAF Val600 mutation were randomly assigned (1:1) by an interactive voice response system to receive either a combination of dabrafenib (150 mg twice-daily) and trametinib (2 mg once-daily) or vemurafenib monotherapy (960 mg twice-daily) orally as first-line therapy. The primary endpoint was overall survival. In this pre-specified exploratory analysis, we prospectively assessed HRQoL in the intention-to-treat population with the European Organisation for Research and Treatment of Cancer quality of life (EORTC QLQ-C30), EuroQoL-5D (EQ-5D), and Melanoma Subscale of the Functional Assessment of Cancer Therapy-Melanoma (FACT-M), completed at baseline, during study treatment, at disease progression, and after progression. We used a mixed-model, repeated measures ANCOVA to assess differences in mean scores between groups with baseline score as covariate; all p-values are descriptive. The COMBI-v trial is registered with ClinicalTrials.gov, number NCT01597908, and is ongoing for the primary endpoint, but is not recruiting patients. Findings: From June 4, 2012, to Oct 7, 2013, 1645 patients at 193 centres worldwide were screened for eligibility, and 704 patients were randomly assigned to dabrafenib plus trametinib (n=352) or vemurafenib (n=352). Questionnaire completion rates for both groups were high (>95% at baseline, >80% at follow-up assessments, and >70% at disease progression) with similar HRQoL and symptom scores reported at baseline in both treatment groups for all questionnaires. Differences in mean scores between treatment groups were significant and clinically meaningful in favour of the combination compared with vemurafenib monotherapy for most domains across all three questionnaires during study treatment and at disease progression, including EORTC QLQ-C30 global health (7·92, 7·62, 6·86, 7·47, 5·16, 7·56, and 7·57 at weeks 8, 16, 24, 32, 40, 48, and disease progression, respectively; p<0·001 for all assessments except p=0·005 at week 40), EORTC QLQ-C30 pain (-13·20, -8·05, -8·82, -12·69, -12·46, -11·41, and -10·57 at weeks 8, 16, 24, 32, 40, 48, and disease progression, respectively; all p<0·001), EQ-5D thermometer scores (7·96, 8·05, 6·83, 11·53, 7·41, 9·08, and 10·51 at weeks 8, 16, 24, 32, 40, 48, and disease progression, respectively; p<0·001 for all assessments except p=0·006 at week 32), and FACT-M Melanoma Subscale score (3·62, 2·93, 2·45, 3·39, 2·85, 3·00, and 3·68 at weeks 8, 16, 24, 32, 40, 48, and disease progression, respectively; all p<0·001). Interpretation: From the patient's perspective, which integrates not only survival advantage but also disease-associated and adverse-event-associated symptoms, treatment with the combination of a BRAF inhibitor plus a MEK inhibitor (dabrafenib plus trametinib) adds a clear benefit over monotherapy with the BRAF inhibitor vemurafenib and supports the combination therapy as standard of care in this population. Funding: GlaxoSmithKline.
    The Lancet Oncology 10/2015; 16(13):1389-1398. DOI:10.1016/S1470-2045(15)00087-X · 24.69 Impact Factor
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    ABSTRACT: Corresponding author. Lab dermatologie, université Reims-Champagne-Ardenne, 51100 Reims, France.
    Annales de Dermatologie et de Vénéréologie 07/2015; 142(6-7). DOI:10.1016/j.annder.2015.04.053 · 0.92 Impact Factor
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    ABSTRACT: Monoclonal T-cell receptor (TCR) rearrangement is detected in 57% to 75% of early-stage mycosis fungoides (MF) at diagnosis. A retrospective study showed molecular residual disease (MRD) in 31% of patients in complete clinical remission (CR) after 1 year of treatment. To confirm the frequency of MRD at 1 year and to determine its prognostic value for further relapse. Patients with T1-, T2- or T4-stage MF were prospectively included in this multicenter study. At diagnosis, clinical lesions and healthy skin were biopsied. After 1 year of topical treatment, previously involved skin (PIS) of patients in CR was biopsied for histology and analysis of TCR-γ gene rearrangement. Results were compared to the clinical status each year for 4 years. We included 214 patients, 133 at T1, 78 T2, and 3 T4 stage. At diagnosis, 126/204 cases (61.8%) showed TCR clonality in lesional skin. After 1 year, 83/178 patients (46.7%) still being followed up were in CR and 13/63 (20.6%) showed MRD. At 4 years, 55/109 (50.5%) patients still being followed up were in CR and 44/109 were in T1 stage (40.4%). MRD did not affect clinical status at 4 years (CR vs. T1/T2, p=1.0, positive predictive value 36.4%, negative predictive value 67.6%). T-cell clonality at diagnosis and MRD at 1 year are not a prognostic factor of clinical status at 4 years. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    British Journal of Dermatology 07/2015; DOI:10.1111/bjd.14017 · 4.28 Impact Factor
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    ABSTRACT: Background Melanoma incidence is increasing worldwide thus justifying information campaigns aimed at reducing ultraviolet exposure levels and promoting early diagnosis.Objectives We set out to assess awareness, knowledge and attitudes of the French population with regard to melanoma prevention and early diagnosis, following more than 15 years of nationwide information campaigns.Methods The French nationwide observational survey, EDIFICE Melanoma, was conducted after the summer (September to October 2011) through structured telephone interviews of a representative sample of 1502 individuals aged ≥18 years, using the quota method. All French regions were represented.ResultsRespondents had heard of sun-induced skin damage: 92% knew that sun increases melanoma risk. Knowledge of sun-protection measures was also good: 97% correctly cited at least one method of photoprotection (clothing 80%, sunscreens 69%) and 97% declared that sun exposure should be reduced between 12 pm and 4 pm in France. Knowledge of melanoma was encouraging: 70% of respondents could define the disease accurately and 60% knew the ABCDE rule for early diagnosis. However, self-tanning and sunbed use were considered by 25% and 13% of respondents, respectively, to provide protection from skin cancer. Although 43% of respondents (58% of high-risk respondents) declared they had consulted a doctor at least once for a suspect skin lesion, their actual behaviour was less encouraging: 30% declared never or almost never protecting their skin; 25% declared regularly checking their skin for atypical nevi; 12% declared checking the entire skin surface. Declared behaviour was better in fair-skin responders and those with a history of sunburn or skin cancer.Conclusions Awareness of melanoma, early-diagnosis procedures and preventive behaviour has improved in the general French population since 1990. However, despite the good level of information, numerous misconceptions persist. Improved information campaigns in the future may help reduce the ever-increasing incidence of melanoma in France.
    Journal of the European Academy of Dermatology and Venereology 02/2015; 29(s2). DOI:10.1111/jdv.12896 · 2.83 Impact Factor
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    ABSTRACT: Background Routine sun protection is recommended to prevent skin cancer. The aims of the present analysis were to assess and compare modalities of sun protection in parents and their children.MethodsEDIFICE Melanoma is a French nationwide observational survey. It was conducted through phone interviews among a representative sample of 1502 individuals aged ≥18 years, using the method of quotas. The survey took place shortly after the summer, from 28 September to 20 October 2011.ResultsOf the 1502 subjects interviewed, 1067 reported sun exposure (SE) at least 10 days per year, 748 were parents and 319 had no children. Sun protection measures seemed adequate in both the ‘parents’ and ‘non-parents’ groups: 74% used clothing and 43% used sunscreen, which was reapplied regularly in 57% of cases. Sun protection measures used by SE parents for SE children were superior, both qualitatively and quantitatively, to those used for themselves, i.e., 50% of parents reported using clothing, sunglasses and hats for their children vs. 23% for themselves. In 87% of cases, parents reported regular re-application of sunscreen for their children vs. 44% for themselves. The sunscreen SPF (Sun Protection Factor) was significantly lower for parents than for their children.Conclusions Sun protection awareness appears to be globally satisfactory in the French population, with no difference between adults who are parents and those who are not. From both qualitative and quantitative standpoints, French parents use sun protective measures more efficiently for their children than for themselves.
    Journal of the European Academy of Dermatology and Venereology 02/2015; 29(s2). DOI:10.1111/jdv.12897 · 2.83 Impact Factor
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    ABSTRACT: Background In addition to natural sunlight, indoor tanning has emerged as a common source of ultraviolet (UV) radiation associated with an increased risk of melanoma. It is classified as a class I human carcinogen by the World Health Organization.Objectives This analysis presents data on the prevalence of sunbed use in France, on factors associated with sunbed use, and on risk factors, attitude and awareness of risk among sunbed users and non-users.Methods Edifice Melanoma, a nationwide observational survey, was conducted in France via telephone interviews among a representative sample of 1502 subjects aged ≥18 years, using the quota method. Sunbed users were defined as individuals who reported having used a sunbed at least once in their lifetime. Logistical regressions were conducted in order to identify which factors differentiate the population of sunbed users from that of non-users.ResultsOne in ten respondents was a sunbed user and three out of four declared having used tanning facilities for over one year. In multivariate analysis, factors significantly associated with the sunbed-user group were female gender (OR = 3.897 [2.573–5.903], P < 0.001), a higher socio-professional category (OR = 2.227 [1.542–3.217]; P < 0.001), fair hair (OR = 1.583 [1.025–2.447], P = 0.039), fair skin (OR = 1.879 [1.086–3.253]; P = 0.024), freckles (OR = 1.570 [1.071–2.302]; P = 0.021) and a history of smoking (OR = 2.383 [1.633–3.476]; P < 0.001). In a second multivariate model, the fact of having a large number of melanoma risk factors was strongly associated with sunbed use (P = 0.001). Sunbed users were more likely to be informed of the role of sun exposure in reducing the skin's regenerative capacity (OR = 2.181 [1.319–3.607]; P = 0.002) but were nevertheless more likely to consider that a tan makes a person look more attractive (OR = 2.309 [1.312–4.064]; P = 0.004) and protects the skin (OR = 2.490 [1.532–4.046]; P < 0.001); they were also more frequently exposed to natural sunlight (OR = 2.214 [1.196–4.102]; P = 0.011).Conclusions Compared to non-users, sunbed users cumulate risk factors for melanoma. Knowledge, attitudes and intentions of individuals are critical targets for public education programmes. However, awareness campaigns focusing on sunbed use, and more generally on skin cancer, should also take social and cultural norms into account.
    Journal of the European Academy of Dermatology and Venereology 02/2015; 29(s2). DOI:10.1111/jdv.12899 · 2.83 Impact Factor
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    ABSTRACT: Background The efficiency of skin cancer prevention programmes is strongly correlated with the information dispensed, and with the level of risk awareness, of the overall population on one hand, and on the other, of specific sub-populations, according to their risk profiles.Objectives The primary objective of this analysis was to establish a correlation between individual perceptions of the risk of developing a melanoma, and the recognized intrinsic risk factors for a given individual. Secondary objectives were to assess factors that are potentially associated with acceptable, high or low perception of melanoma risk.Methods The EDIFICE Melanoma survey was conducted in 2011 via telephone interviews of a representative sample of 1502 individuals aged 18 and older in the French population.ResultsAlthough most respondents (73%) had a true estimation of their intrinsic risk for melanoma, those who did not (underestimation, 17%; overestimation, 10%) had an attitude towards environmental risk factors (sun exposure, sun protection, sunbed use) that did not compensate for this misplaced perception.Conclusions Skin cancer prevention messages need to be reinforced, new methods of evaluating understanding of the messages need to be implemented, and both need to be included into personal risk assessment.
    Journal of the European Academy of Dermatology and Venereology 02/2015; 29(s2). DOI:10.1111/jdv.12900 · 2.83 Impact Factor
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    ABSTRACT: Objectives: The incidence of skin cancers, melanoma in particular, is increasing rapidly. Consequently, specific recommendations for sun-protection measures now exist. This survey set out to assess the compliance of the general population with these guidelines. Methods: The French nationwide observational survey, EDIFICE Melanoma, was conducted (28 September to 20 October 2011) through phone interviews of a representative sample of 1502 subjects aged ≥ 18 years, using the quota method. Sun-protection was defined as frequent or systematic use of clothes or sunscreen. The group of individuals who declared exposure to the sun (N = 1172) was subdivided: risk-takers (N = 442), and those who used sun protection (N = 730). Results: Risk-takers were significantly more often male (62% vs. 44%, P < 0.01), had a lower level of education (40% vs. 26%, P < 0.01), lower incomes (2587 euros vs. 2948 euros/month) and were more often smokers (42% vs. 31%, P < 0.01). In contrast, age, marital status and use of sunbeds were not significantly different between the two groups. Interestingly, risk-takers had less risk factors for melanoma. However, they were less well-informed about high-risk exposure and optimal use of sunscreen. Sun-protection measures for their children were less stringent than those of the group who used sun protection: systematic/frequent use of sunglasses (42% vs. 59%, P < 0.01), systematic use of sunscreen (77% vs. 86%, P < 0.01), and frequent renewal (69% vs. 82%, P < 0.01), high sun protection factors (SPF) (46% vs. 56%, P < 0.01), use of clothing (84% vs. 92%, P < 0.01) and hats (88% vs. 94%, P < 0.01). Conclusions: Risk-takers are characterized by a lesser understanding of sun-protection measures and behaviours. Their children benefit less from protective measures than those of people who use sun protection themselves. Improved understanding may well improve behaviours; one can therefore legitimately predict a considerable impact on parents' attitude to their own protection and that of their children.
    Journal of the European Academy of Dermatology and Venereology 02/2015; 29(s2). DOI:10.1111/jdv.12901 · 2.83 Impact Factor
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    ABSTRACT: Background The incidence of melanoma is increasing worldwide, causing significant economic burden at community and individual levels. Ultraviolet radiation, from natural sunlight or artificial sources, is the main environmental, modifiable risk factor for melanoma.Objectives The present analysis assesses the profile of sun exposure in the French population as well as the level of awareness about ultraviolet risk and protection.Methods The survey was conducted via telephone interviews in September and October 2011. In total, 1502 respondents were questioned about their own sun exposure with the question “do you ever, even occasionally, spend time in the sun, during leisure-time, vacation or your professional occupation?” They were also asked about sun protection measures used: protective clothing, a hat or sunscreen.ResultsMore than three respondents out of four (78%) declared exposing themselves to the sun, with an average of 113 days per year. Of these, 38% did not use appropriate sun protection measures. We identified the following characteristics of individuals declaring high sun exposure: chiefly men under the age of 40, higher socio-professional levels, and adults with no children. Individuals who make a poor use of protective measures are mostly men and of low educational levels. Individuals declaring low sun exposure were chiefly: women, individuals over the age of 60, and those with no professional activity. The high sun protection population comprises mostly: women, higher socio-professional levels, with no specific age-group profile.Conclusions Analysis of the EDIFICE Melanoma survey provides information about the attitudes of the French population towards sun exposure. The most frequent contexts of sun exposure and the associated socio-demographic characteristics of the population with at-risk attitudes regarding sun exposure are identified. This deeper insight into the profile of at-risk populations will allow interventions to be more accurately targeted, thus potentially improving public health benefits.
    Journal of the European Academy of Dermatology and Venereology 02/2015; 29(s2). DOI:10.1111/jdv.12895 · 2.83 Impact Factor
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    ABSTRACT: Background The prevention of melanoma can be significantly improved by targeting information directly towards the subpopulation of children and, as a means to achieve it, towards young parents.Objectives The objective of this analysis was to determine the evolution over time of the sun-protection measures adopted by parents for their young children.Methods The Edifice Melanoma survey was based on telephone interviews of a representative sample of 1502 subjects aged ≥18 years. This particular analysis focuses on 864 adults whose children are exposed to the sun for more than 10 days a year. We compared the characteristics and attitudes of two sub-groups of parents with regard to sun protection of young children: current-day behaviour of parents with children <15 years and behaviour in the past of parents whose children are now ≥15 years.ResultsPresent-day parents are more likely than those of previous generations to systematically or often use hats (96% vs. 90%, P < 0.01), protective clothes (92% vs. 84%, P < 0.01), sunscreen (89% vs. 80%, P < 0.01) and sunglasses (63% vs. 44%, P < 0.01) for their children. Systematic application of sunscreen is also more frequent today than several years ago as reported by 81% of present-day parents vs. 74% of those in the past (P < 0.05). Cream is reapplied every 2 h by 41% of present-day parents, compared to 33%, in the past (P < 0.05).Conclusions The attitude of parents towards sun protection for their children has improved over the past decade.
    Journal of the European Academy of Dermatology and Venereology 02/2015; 29(s2). DOI:10.1111/jdv.12898 · 2.83 Impact Factor
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    ABSTRACT: Iconographie disponible sur CD et Internet.
    Annales de Dermatologie et de Vénéréologie 12/2014; 141(12):S350. DOI:10.1016/j.annder.2014.09.283 · 0.92 Impact Factor
  • Annales de Dermatologie et de Vénéréologie 12/2014; 141(12):S257-S258. DOI:10.1016/j.annder.2014.09.082 · 0.92 Impact Factor
  • Annales de Dermatologie et de Vénéréologie 12/2014; 141(12):S386. DOI:10.1016/j.annder.2014.09.359 · 0.92 Impact Factor
  • Annales de Dermatologie et de Vénéréologie 12/2014; 141(12):S286. DOI:10.1016/j.annder.2014.09.138 · 0.92 Impact Factor
  • Annales de Dermatologie et de Vénéréologie 12/2014; 141(12):S288-S289. DOI:10.1016/j.annder.2014.09.143 · 0.92 Impact Factor
  • C. Duretz · F. Grange · P. Bernard · A. Grange
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    ABSTRACT: Iconographie disponible sur CD et Internet.
    Annales de Dermatologie et de Vénéréologie 12/2014; 141(12):S407. DOI:10.1016/j.annder.2014.09.403 · 0.92 Impact Factor
  • Annales de Dermatologie et de Vénéréologie 12/2014; 141(12):S254-S255. DOI:10.1016/j.annder.2014.09.076 · 0.92 Impact Factor

Publication Stats

4k Citations
543.10 Total Impact Points


  • 2005–2015
    • Hôpital Universitaire Robert Debré
      Lutetia Parisorum, Île-de-France, France
    • Université de Reims Champagne-Ardenne
      • Laboratoire SiRMa
      Rheims, Champagne-Ardenne, France
  • 2005–2014
    • Centre Hospitalier Universitaire de Reims
      • Service de Dermatologie
      Rheims, Champagne-Ardenne, France
  • 1995–2013
    • Institut de Cancérologie Gustave Roussy
      • Department of Radiotherapy
      Villejuif, Île-de-France, France
  • 2011
    • Hôpital Louis Pradel
      Lyons, Rhône-Alpes, France
  • 2010
    • Centre Hospitalier Universitaire de Bordeaux
      Burdeos, Aquitaine, France
  • 1997–2008
    • Hopitaux Civils De Colmar
      Kolmar, Alsace, France
  • 2002
    • IST Austria
      Klosterneuberg, Lower Austria, Austria
  • 2000
    • Université Victor Segalen Bordeaux 2
      Burdeos, Aquitaine, France