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Melanoma: HELP
Articles by Luis de la Cruz-Merino
Based on 11 articles published since 2008
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Between 2008 and 2019, L. De La Cruz Merino wrote the following 11 articles about Melanoma.
 
+ Citations + Abstracts
1 Review Advances in the Immunobiological Therapies for Advanced Melanoma. 2017

Pérez Gago, M C / Saavedra Santa Gadea, O / de la Cruz-Merino, L. ·Servicio de Oncología Médica, Hospital Universitario Virgen Macarena, Sevilla, España. · Servicio de Oncología Médica, Hospital Universitario Virgen Macarena, Sevilla, España. Electronic address: ldelacruzmerino@gmail.com. ·Actas Dermosifiliogr · Pubmed #28388991.

ABSTRACT: Metastatic or locally advanced unresectable melanoma carries a high morbidity and mortality. However, notable advances have been made in recent years in the systemic treatment of this disease, with the appearance of targeted therapy using tyrosine kinase inhibitors that block the mitogen activated protein kinase pathway, and of modern immunotherapy with immune-modulating monoclonal antibodies. In this paper, we provide an update of available data on new immune therapies and we review the clinical development that led to their approval for use in routine clinical practice.

2 Review Isolated limb perfusion for malignant melanoma: systematic review on effectiveness and safety. 2010

Moreno-Ramirez, David / de la Cruz-Merino, Luis / Ferrandiz, Lara / Villegas-Portero, Roman / Nieto-Garcia, Adoracion. ·Melanoma Unit, Dermatology Department, Hospital Universitario Virgen Macarena, Seville, Spain. dmoreno@e-derma.org ·Oncologist · Pubmed #20348274.

ABSTRACT: BACKGROUND: Isolated limb perfusion (ILP) involves the administration of chemotherapy drugs directly into a limb involved by locoregional metastases. Unresectable locally advanced melanoma of the limbs represents one of the clinical settings in which ILP has demonstrated benefits. METHODS: A systematic review of the literature on ILP for patients with unresectable locally advanced melanoma of the limbs was conducted. MEDLINE, EMBASE, and Cochrane database searches were conducted to identify studies fulfilling the following inclusion criteria: hyper- or normothermic ILP with melphalan with or without tumor necrosis factor (TNF) or other drugs providing valid data on clinical response, survival, or toxicity. To allocate levels of evidence and grades of recommendation the Scottish Intercollegiate Guidelines Network system was used. RESULTS: Twenty-two studies including 2,018 ILPs were selected with a clear predominance of observational studies (90.90%) against experimental studies (9.10%). The median complete response rate to ILP was of 58.20%, with a median overall response rate of 90.35%. ILP with melphalan yielded a median complete response rate of 46.50%, against a 68.90% median complete response rate for melphalan plus TNF ILP. The median 5-year overall-survival rate was 36.50%, with a median overall survival interval of 36.70 months. The Wieberdink IV and V regional toxicity rates were 2.00% and 0.65%, respectively. CONCLUSIONS: ILP is effective in achieving clinical responses in patients with unresectable locally advanced melanoma of the limbs. The disease-free and overall survival rates provided by ILP are acceptable. ILP is safe, with a low incidence of severe regional and systemic toxicity.

3 Clinical Trial Health-related quality of life impact of cobimetinib in combination with vemurafenib in patients with advanced or metastatic BRAF 2018

Dréno, Brigitte / Ascierto, Paolo A / Atkinson, Victoria / Liszkay, Gabriella / Maio, Michele / Mandalà, Mario / Demidov, Lev / Stroyakovskiy, Daniil / Thomas, Luc / de la Cruz-Merino, Luis / Dutriaux, Caroline / Garbe, Claus / Bartley, Karen / Karagiannis, Thomas / Chang, Ilsung / Rooney, Isabelle / Koralek, Daniel O / Larkin, James / McArthur, Grant A / Ribas, Antoni. ·Department of Dermato Cancerology, Nantes University, Nantes 44093, France. · Istituto Nazionale Tumori Fondazione G. Pascale, Naples 80131, Italy. · Princess Alexandra Hospital, Woolloongabba, QLD 4102, Australia. · National Institute of Oncology, Budapest 1122, Hungary. · Azienda Ospedaliera Universitaria Senese, Siena 53100, Italy. · Department of Oncology and Haematology, Papa Giovanni XXIII Hospital, Bergamo 24127, Italy. · N. N. Blokhin Russian Cancer Research Center, Moscow 115478, Russia. · Moscow City Oncology Hospital 62, Krasnogorsk 14301, Russia. · Service de Dermatologie, Centre Hospitalier Lyon Sud, Pierre-Bénite 69495, France. · Hospital Universitario Virgen Macarena, Seville 41009, Spain. · Hôpital Saint André, Bordeaux 33075, France. · Department of Dermatology, University of Tübingen, Tübingen 72074, Germany. · Genentech, Inc., South San Francisco, CA 94080, USA. · The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK. · Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia. · University of Melbourne, Parkville, VIC 3052, Australia. · Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA 90095, USA. ·Br J Cancer · Pubmed #29438370.

ABSTRACT: BACKGROUND: In the coBRIM study, cobimetinib plus vemurafenib (C+V) significantly improved survival outcomes vs placebo and vemurafenib (P+V) in patients with advanced/metastatic BRAF METHODS: Patients completing the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30) at baseline and ⩾1 time point thereafter constituted the analysis population. Change from baseline ⩾10 points was considered clinically meaningful. RESULTS: Mean baseline scores for all QLQ-C30 domains were similar between arms. Most on-treatment scores for QLQ-C30 domains were also comparable between arms. A transient deterioration in role function in cycle 1 day 15 (C1D15; -14.7 points) in the P+V arm and improvement in insomnia in the C+V arm at C2D15 (-12.4 points) was observed. Among patients who experienced a ⩾10-point change from baseline (responders), between-group differences were greatest for insomnia (16%), social functioning (10%), fatigue (9%) and pain (7%), all favouring C+V. Diarrhoea, photosensitivity reaction, pyrexia, and rash did not meaningfully affect global health status (GHS). Serous retinopathy was associated with a transient decrease in GHS at C1D15 assessment. CONCLUSIONS: In patients with advanced/metastatic BRAF

4 Clinical Trial Cobimetinib combined with vemurafenib in advanced BRAF(V600)-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial. 2016

Ascierto, Paolo A / McArthur, Grant A / Dréno, Brigitte / Atkinson, Victoria / Liszkay, Gabrielle / Di Giacomo, Anna Maria / Mandalà, Mario / Demidov, Lev / Stroyakovskiy, Daniil / Thomas, Luc / de la Cruz-Merino, Luis / Dutriaux, Caroline / Garbe, Claus / Yan, Yibing / Wongchenko, Matthew / Chang, Ilsung / Hsu, Jessie J / Koralek, Daniel O / Rooney, Isabelle / Ribas, Antoni / Larkin, James. ·Istituto Nazionale Tumori Fondazione G Pascale, Naples, Italy. · Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia; University of Melbourne, Parkville, VIC, Australia. Electronic address: grant.mcarthur@petermac.org. · Nantes University, Nantes, France. · Princess Alexandra Hospital, Woolloongabba, QLD, Australia. · National Institute of Oncology, Budapest, Hungary. · Azienda Ospedaliera Universitaria Senese, Siena, Italy. · Papa Giovanni XXIII Hospital, Bergamo, Italy. · N N Blokhin Russian Cancer Research Center, Moscow, Russia. · Moscow City Oncology Hospital 62, Krasnogorsk, Russia. · Centre Hospitalier Lyon Sud, Lyon 1 University, Lyon, France; Lyons Cancer Research Center, Lyon, France. · Hospital Universitario Virgen Macarena, Seville, Spain. · Hôpital Saint André, Bordeaux, France. · University of Tübingen, Tübingen, Germany. · Genentech Inc, South San Francisco, CA, USA. · Jonsson Comprehensive Cancer Center at University of California, Los Angeles, Los Angeles, CA, USA. · Royal Marsden NHS Foundation Trust, London, UK. ·Lancet Oncol · Pubmed #27480103.

ABSTRACT: BACKGROUND: The combination of cobimetinib with vemurafenib improves progression-free survival compared with placebo and vemurafenib in previously untreated patients with BRAF(V600)-mutant advanced melanoma, as previously reported in the coBRIM study. In this Article, we report updated efficacy results, including overall survival and safety after longer follow-up, and selected biomarker correlative studies. METHODS: In this double-blind, randomised, placebo-controlled, multicentre study, adult patients (aged ≥18 years) with histologically confirmed BRAF(V600) mutation-positive unresectable stage IIIC or stage IV melanoma were randomly assigned (1:1) using an interactive response system to receive cobimetinib (60 mg once daily for 21 days followed by a 7-day rest period in each 28-day cycle) or placebo, in combination with oral vemurafenib (960 mg twice daily). Progression-free and overall survival were primary and secondary endpoints, respectively; all analyses were done on the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01689519, and is ongoing but no longer recruiting participants. FINDINGS: Between Jan 8, 2013, and Jan 31, 2014, 495 eligible adult patients were enrolled and randomly assigned to the cobimetinib plus vemurafenib group (n=247) or placebo plus vemurafenib group (n=248). At a median follow-up of 14·2 months (IQR 8·5-17·3), the updated investigator-assessed median progression-free survival was 12·3 months (95% CI 9·5-13·4) for cobimetinib and vemurafenib versus 7·2 months (5·6-7·5) for placebo and vemurafenib (HR 0·58 [95% CI 0·46-0·72], p<0·0001). The final analysis for overall survival occurred when 255 (52%) patients had died (Aug 28, 2015). Median overall survival was 22·3 months (95% CI 20·3-not estimable) for cobimetinib and vemurafenib versus 17·4 months (95% CI 15·0-19·8) for placebo and vemurafenib (HR 0·70, 95% CI 0·55-0·90; p=0·005). The safety profile for cobimetinib and vemurafenib was tolerable and manageable, and no new safety signals were observed with longer follow-up. The most common grade 3-4 adverse events occurring at a higher frequency in patients in the cobimetinib and vemurafenib group compared with the vemurafenib group were γ-glutamyl transferase increase (36 [15%] in the cobimetinib and vemurafenib group vs 25 [10%] in the placebo and vemurafenib group), blood creatine phosphokinase increase (30 [12%] vs one [<1%]), and alanine transaminase increase (28 [11%] vs 15 [6%]). Serious adverse events occurred in 92 patients (37%) in the cobimetinib and vemurafenib group and 69 patients (28%) in the vemurafenib group. Pyrexia (six patients [2%]) and dehydration (five patients [2%]) were the most common serious adverse events reported in the cobimetinib and vemurafenib group. A total of 259 patients have died: 117 (47%) in the cobimetinib and vemurafenib group and 142 (58%) in the vemurafenib group. The primary cause of death was disease progression in most patients: 109 (93%) of 117 in the cobimetinib and vemurafenib group and 133 (94%) of 142 in the vemurafenib group. INTERPRETATION: These data confirm the clinical benefit of cobimetinib combined with vemurafenib and support the use of the combination as a standard first-line approach to improve survival in patients with advanced BRAF(V600)-mutant melanoma. FUNDING: F Hoffmann-La Roche-Genentech.

5 Clinical Trial Safety of vemurafenib in patients with BRAF 2016

Arance, A M / Berrocal, A / Lopez-Martin, J A / de la Cruz-Merino, L / Soriano, V / Martín Algarra, S / Alonso, L / Cerezuela, P / La Orden, B / Espinosa, E. ·Hospital Clínic and Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. AMARANCE@clinic.ub.es. · Hospital General Universitario de Valencia, Valencia, Spain. · Hospital Universitario 12 de Octubre, Madrid, Spain. · Hospital Univ. Virgen de la Macarena de Sevilla, Seville, Spain. · Instituto Valenciano de Oncología, Valencia, Spain. · Clínica Universidad de Navarra, Navarra, Spain. · Hospital Clínico de Málaga, Malaga, Spain. · Hospital Universitario Santa Lucía de Cartagena, Cartagena, Spain. · Roche Farma, Madrid, Spain. · Hospital Universitario La Paz, Madrid, Spain. ·Clin Transl Oncol · Pubmed #26983408.

ABSTRACT: OBJECTIVES: Vemurafenib tolerability was assessed in a large, open-label, multicentre study in patients with BRAF METHODS: Patients with previously treated or treatment-naive, unresectable stage IIIC or stage IV, BRAF RESULTS: 301 Spanish patients were included, 70 % with M1c disease, 22 % with brain metastases and 51 % with prior systemic therapy for metastatic disease. Most frequent adverse events included fatigue (48 %), arthralgia (45 %), rash (41 %), photosensitivity (34 %) and skin neoplasms (21 %). Grade 3/4 adverse events occurred in 156 patients (52 %), including cutaneous squamous cell carcinoma (including keratoacanthoma; 16 %), fatigue (6 %) and arthralgia (5 %). The ORR was 28 % (95 % CI 23-34 %). Responses occurred in patients with brain metastases (18 %), elevated baseline lactate dehydrogenase (19 %) and poor performance status (15 %), and elderly patients (22 %). Median PFS was 5.8 (95 % CI 5.0-6.4) months; median OS was 10.5 (95 % CI 9.5-13.5) months. CONCLUSION: Our results for Spanish patients in the vemurafenib safety study indicate similar efficacy and a comparable safety profile in Spanish patients with no new safety signals compared with the overall population. Clinical benefit was demonstrated in poor-prognosis patients and in those with favourable baseline characteristics, suggesting that poor-prognosis patients may also benefit from vemurafenib treatment.

6 Clinical Trial Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. 2014

Larkin, James / Ascierto, Paolo A / Dréno, Brigitte / Atkinson, Victoria / Liszkay, Gabriella / Maio, Michele / Mandalà, Mario / Demidov, Lev / Stroyakovskiy, Daniil / Thomas, Luc / de la Cruz-Merino, Luis / Dutriaux, Caroline / Garbe, Claus / Sovak, Mika A / Chang, Ilsung / Choong, Nicholas / Hack, Stephen P / McArthur, Grant A / Ribas, Antoni. ·From Royal Marsden Hospital, London (J.L.) · Istituto Nazionale Tumori Fondazione G. Pascale, Naples (P.A.A.), Azienda Ospedaliera Universitaria Senese, Siena (M. Maio), and Papa Giovanni XXIII Hospital, Bergamo (M. Mandalà) - all in Italy · Hôtel Dieu Place Alexis Ricordeau, Nantes (B.D.), Centre Hospitalier Lyon Sud, Pierre-Bénite (L.T.), and Hôpital Saint André, Bordeaux (C.D.) - all in France · Princess Alexandra Hospital, Woolloongabba, QLD (V.A.), and Peter MacCallum Cancer Centre, Melbourne, VIC (G.A.M.) - both in Australia · National Institute of Oncology, Budapest, Hungary (G.L.) · N.N. Blokhin Russian Cancer Research Center, Moscow (L.D.), and Moscow City Oncology Hospital 62, Krasnogorsk (D.S.) - both in Russia · Hospital Universitario Virgen Macarena, Seville, Spain (L.C.-M.) · University of Tübingen, Tübingen, Germany (C.G.) · Genentech, South San Francisco, CA (M.A.S., I.C., N.C., S.P.H.) · and Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, Los Angeles (A.R.). ·N Engl J Med · Pubmed #25265494.

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. (Funded by F. Hoffmann-La Roche/Genentech; coBRIM ClinicalTrials.gov number, NCT01689519.).

7 Article Clinical features of serous retinopathy observed with cobimetinib in patients with BRAF-mutated melanoma treated in the randomized coBRIM study. 2017

de la Cruz-Merino, Luis / Di Guardo, Lorenza / Grob, Jean-Jacques / Venosa, Alfredo / Larkin, James / McArthur, Grant A / Ribas, Antoni / Ascierto, Paolo A / Evans, Jeffrey T R / Gomez-Escobar, Antonio / Barteselli, Giulio / Eng, Susan / Hsu, Jessie J / Uyei, Anne / Dréno, Brigitte. ·Servicio de Oncología Médica, Hospital Universitario Virgen Macarena, Avenida Doctor Fedriani 3, 41071, Seville, Spain. lucme12@yahoo.es. · Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. · Aix-Marseille University, Hôpital de la Timone, Marseille, France. · Ospedale Monaldi, Naples, Italy. · Royal Marsden NHS Foundation Trust, London, UK. · Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia. · University of Melbourne, Parkville, VIC, Australia. · Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, CA, USA. · Istituto Nazionale Tumori Fondazione G. Pascale, Naples, Italy. · Beatson West of Scotland Cancer Centre, University of Glasgow, Glasgow, UK. · Servicio de Oncología Médica, Hospital Universitario Virgen Macarena, Avenida Doctor Fedriani 3, 41071, Seville, Spain. · Genentech, Inc., South San Francisco, CA, USA. · Nantes University, Nantes, France. ·J Transl Med · Pubmed #28646893.

ABSTRACT: BACKGROUND: Serous chorioretinopathy has been associated with MEK inhibitors, including cobimetinib. We describe the clinical features of serous retinopathy observed with cobimetinib in patients with BRAF METHODS: In the coBRIM study, 493 patients were treated in two randomly assigned treatment groups: cobimetinib and vemurafenib (n = 247) or vemurafenib (n = 246). All patients underwent prospective ophthalmic examinations at screening, at regular intervals during the study, and whenever ocular symptoms developed. Patients with serous retinopathy were identified in the study database using a group of relevant and synonymous adverse event terms. RESULTS: Eighty-six serous retinopathy events were reported in 70 patients (79 events in 63 cobimetinib and vemurafenib-treated patients vs seven events in seven vemurafenib-treated patients). Most patients with serous retinopathy identified by ophthalmic examination had no symptoms or had mild symptoms, among them reduced visual acuity, blurred vision, dyschromatopsia, and photophobia. Serous retinopathy usually occurred early during cobimetinib and vemurafenib treatment; median time to onset was 1.0 month. Most events were managed by observation and continuation of cobimetinib without dose modification and resolved or were resolving by the data cutoff date (19 Sept 2014). CONCLUSIONS: Cobimetinib treatment was associated with serous retinopathy in patients with BRAF

8 Article More than 5000 patients with metastatic melanoma in Europe per year do not have access to recommended first-line innovative treatments. 2017

Kandolf Sekulovic, L / Peris, K / Hauschild, A / Stratigos, A / Grob, J-J / Nathan, P / Dummer, R / Forsea, A-M / Hoeller, C / Gogas, H / Demidov, L / Lebbe, C / Blank, C / Olah, J / Bastholt, L / Herceg, D / Neyns, B / Vieira, R / Hansson, J / Rutkowski, P / Krajsova, I / Bylaite-Bucinskiene, M / Zalaudek, I / Maric-Brozic, J / Babovic, N / Banjin, M / Putnik, K / Weinlich, G / Todorovic, V / Kirov, K / Ocvirk, J / Zhukavets, A / Kukushkina, M / De La Cruz Merino, L / Ymeri, A / Risteski, M / Garbe, C. ·Department of Dermatology, Medical Faculty, Military Medical Academy, Belgrade, Serbia. · Institute of Dermatology, Catholic University of the Sacred Heart, Rome, Italy. · Department of Dermatology, University Hospital Schleswig-Holstein (UKSH), Campus Kiel, Kiel, Germany. · National and Kapodistrian University of Athens, Greece. · Service de Dermatologie et Cancérologie Cutanée, Hopital de la Timone, Marseille, France. · Mount Vernon Cancer Centre, Northwood, United Kingdom. · UniversitätsSpital Zürich-Skin Cancer Center, University Hospital, Zürich, Switzerland. · Carol Davila University of Medicine and Pharmacy, Elias University Hospital Bucharest, Romania. · Department of Dermatology, Medical University of Vienna, Vienna, Austria. · NN Blokhin Russian Cancer Research Center, Moscow, Russia. · APHP Hospital Saint Louis, Paris, France. · Netherland Cancer Institute, Amsterdam, Netherlands. · Department of Dermatology and Allergology, University of Szeged, Hungary. · Department of Oncology, Odense University Hospital, Denmark. · Department of Oncology, University Hospital Zagreb, Croatia. · Department of Medical Oncology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel (VUB), Brussels, Belgium. · Department of Dermatology, Medical Faculty, University of Coimbra, Portugal. · Department of Oncology-Pathology, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden. · Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warszawa, Poland. · General Teaching Hospital, Prague, Czech Republic. · Department of Dermatology, Vilnius University, Lithuania. · Division of Dermatology and Venerology, Medical University of Graz, Graz, Austria. · University Hospital Center Sestre Milosrdnice, Zagreb, Croatia. · Institute of Oncology and Radiology of Serbia, Belgrade, Serbia. · Department of Oncology, University Hospital Sarajevo, Bosnia and Herzegovina. · North Estonia Medical Centre, Tallinn, Estonia. · Department of Dermatology & Venerology & Allergy, Medical University Innsbruck, Austria. · Clinic for Oncology and Radiotherapy, Podgorica, Montenegro. · Clinic of Oncodermatology, National Cancer Center, Sofia, Bulgaria. · Institute of Oncology Ljubljana, Ljubljana, Slovenia. · N.N. Alexandrov National Cancer Сenter of Belarus (NCCB), Minsk, Belarus. · National Cancer Institute, Kiev, Ukraine. · Department of Clinical Oncology, Hospital Universitario Virgen Macarena, Sevilla, Spain. · University Hospital Mother Theresa, Tirana, Albania. · University Clinic of Radiotherapy and Oncology, Skopje, Former Yugoslav Republic of Macedonia. · Centre for Dermatooncology, Department of Dermatology, Eberhard Karls University, Tuebingen, Germany. ·Eur J Cancer · Pubmed #28264791.

ABSTRACT: BACKGROUND: Despite the efficacy of innovative treatments for metastatic melanoma, their high costs has led to disparities in cancer care among different European countries. We analysed the availability of these innovative therapies in Europe and estimated the number of patients without access to first-line recommended treatment per current guidelines of professional entities such as the European Society for Medical Oncology (ESMO), the European Organisation for Research and Treatment of Cancer (EORTC), the European Association of Dermato-Oncology (EADO), and European Dermatology Forum (EDF). MATERIALS AND METHODS: Web-based online survey was conducted in 30 European countries with questions about the treatment schedules from 1st May 2015 to 1st May 2016: number of metastatic melanoma patients, registration and reimbursement of innovative medicines (updated data, as of 1st October 2016), percentage of patients treated and availability of clinical studies and compassionate-use programmes. RESULTS: The recommended BRAF inhibitor (BRAFi) + MEK inhibitor (MEKi) combination was both registered and fully reimbursed in 9/30 (30%) countries, and in 13/30 (43%) (all from Eastern Europe) not reimbursed. First-line immunotherapy with anti-PD1 antibodies was registered and fully reimbursed in 14/30 (47%) countries, while in 13/30 (43%) (all from Eastern Europe) not reimbursed. It was estimated that in Europe 19,600 patients with metastatic melanoma are treated, and 5238 (27%) do not have access to recommended first-line therapy. Significant correlation was found between human development index (HDI, UNDP report 2015), (r = 0.662; p < 0.001), health expenditure per capita (r = 0.695; p < 0.001) and the Mackenbach score of health policy performance (r = 0.765; p < 0.001) with the percentage of patients treated with innovative medicines and a number of reimbursed medicines. CONCLUSIONS: Great discrepancy exists in metastatic melanoma treatment across Europe. It is crucial to increase the awareness of national and European policymakers, oncological societies, melanoma patients' associations and pharma industry.

9 Article Treatment patterns of adjuvant interferon-α2b for high-risk melanoma: a retrospective study of the Grupo Español Multidisciplinar de Melanoma - Prima study. 2016

Espinosa, Enrique / Soriano, Virtudes / Malvehy, Josep / Berrocal, Alfonso / Martínez de Prado, Purificación / Quindós, María / Soria, Ainara / Márquez-Rodas, Iván / Palacio, Isabel / Cerezuela, Pablo / López-Vivanco, Guillermo / Alonso, Lorenzo / Samaniego, Elia / Ballesteros, Ana / Puértolas, Teresa / Díaz-Beveridge, Rodrigo / de la Cruz-Merino, Luis / López Castro, Rafael / López López, Rafael / Stevinson, Kendall / Del Barrio, Patricia / Tornamira, Maria V / Guillém, Vicente / Martín-Algarra, Salvador. ·aMedical Oncology Service, Hospital Universitario La Paz bMedical Oncology Service, Hospital Ramón y Cajal cMedical Oncology Service, Instituto de Investigación Sanitaria Gregorio Marañon dMedical Oncology Service, Hospital La Princesa eMedical Affairs, Merck Sharp & Dohme, Madrid fMedical Oncology Service, Instituto Valenciano de Oncología gMedical Oncology Service, Hospital General Universitario de Valencia hMedical Oncology Service, Hospital La Fe, Valencia iMedical Oncology Service, Hospital Clinic de Barcelona, Barcelona jMedical Oncology Service, Hospital de Basurto, Bilbao kMedical Oncology Service, Hospital Teresa Herrera, La Coruña lMedical Oncology Service, Hospital Central de Asturias, Oviedo mMedical Oncology Service, Hospital General Universitario Santa Lucía, Cartagena nMedical Oncology Service, Hospital de Cruces, San Vicente de Baracaldo oMedical Oncology Service, Hospital Universitario Virgen de la Victoria, Málaga pDermatology Service, Complejo Asistencial Universitario de León, León qMedical Oncology Service, Hospital Miguel Servet, Zaragoza rMedical Oncology Service, Hospital Virgen de la Macarena, Sevilla sMedical Oncology Service, Hospital Clínico Universitario de Valladolid, Valladolid tMedical Oncology Service, Hospital Clínico Universitario de Santiago, Santiago de Compostela uMedical Oncology Service, Clínica Universitaria de Navarra, Pamplona, Spain vGlobal Health Outcomes Research, Merck Sharp & Dohme, Kenilworth, New Jersey, USA. ·Melanoma Res · Pubmed #26958991.

ABSTRACT: Adjuvant interferon-α2b (IFN-α2b) has been studied extensively in clinical trials, but there have been few studies of real-world use. The aim of this study is to describe the IFN-α2b real-world patterns in patients with high-risk melanoma in Spain. This was a retrospective and multicentre chart review study of an unselected cohort of patients with melanoma at high risk for relapse (stage IIB/IIC/III) treated with IFN-α2b. Patterns were assessed in terms of dose and compliance to planned treatment. A survival analysis was carried out for the full population and according to Kirkwood scheme compliance and the presence of ulceration. Of 327 patients treated with IFN-α2b, 318 received a high-dose regimen following the standard Kirkwood scheme; thus, patterns are described for this regimen. A total of 121 (38%) and 88 (28%) patients had at least one dose reduction during the induction and maintenance phases, respectively. Dose delay was required in fewer than 10% of patients. A total of 78, 40 and 38% of the patients completed the induction phase, maintenance phase and completed treatment, respectively. The median progression-free and overall survival for the full population were 3.2 and 10.5 years, respectively. There were no differences in progression-free survival and overall survival according to Kirkwood scheme compliance and the presence of ulceration. The most frequent adverse events were neutropenia (31%) and fatigue (30%). High-dose IFN-α2b is the most frequently used regimen in Spain as an adjuvant systemic treatment for high-risk melanoma. Despite poor compliance, in this retrospective study, IFN-α2b treatment provided a benefit consistent with that described previously.

10 Article Clinical use of ipilimumab for metastatic melanoma in Spain: towards a more consistent approach. 2016

Martín-Algarra, S / de la Cruz-Merino, L / Soriano, V / Manzano, J L / Espinosa, E. ·Department of Oncology, Clínica Universidad de Navarra. Instituto de Investigación Sanitaria de Navarra (IDISNA), Av. Pío XII, 36, 31008, Pamplona, Navarra, España, Spain. smalgarra@unav.es. · Department of Clinical Oncology, Hospital Virgen Macarena, Seville, Spain. · Department of Oncology, Instituto Valenciano Oncología, Valencia, Spain. · Department of Oncology, Hospital Germans Trias i Pujol. ICO-Badalona, Barcelona, Spain. · Department of Oncology, Hospital La Paz, Madrid, Spain. ·Clin Transl Oncol · Pubmed #26801342.

ABSTRACT: INTRODUCTION: Ipilimumab has been approved in patients with advanced melanoma by different regulatory bodies worldwide, but its use in clinical practice is not fully consistent among oncologists. We have surveyed a representative sample of Spanish medical oncologists on issues related to the use of ipilimumab. MATERIALS AND METHODS: The survey was based on the Delphi method, where experts respond anonymously to two rounds of a questionnaire. Questionnaire consisted of 42 statements divided among the following eight categories: Pathology and Diagnosis; Patterns of Response; Parameters affecting Treatment Selection; Patient Profile; Sequencing of Treatment; Definition of Long-Term Survivors; Quality of Life; Concept of Immuno-oncology. The experts were asked to rate each statement on a scale of 1-9, where 1 meant "completely disagree" and 9 meant "completely agree". RESULTS: Thirty-three oncologists responded to both rounds of the survey (62.3 % of total surveyed). On issues related to pathology and diagnosis, patterns of response, and immuno-oncology, the specialists reached a high level of consensus. There was also a high level of agreement, albeit without consensus on assessment of BRAF mutations before deciding on treatment with ipilimumab. However, there was a lower level of agreement on sequencing treatment with BRAF inhibitors and ipilimumab, on predictive factors, on the use of corticosteroids, and on patient quality of life. CONCLUSIONS: The disparity in many of these topics suggests that oncologists need more information on certain aspects of ipilimumab treatment. We need to define generally accepted algorithms of treatment, especially with regard to issues that were shown to be controversial or unclear.

11 Article Frequency and characteristics of familial melanoma in Spain: the FAM-GEM-1 Study. 2015

Márquez-Rodas, Iván / Martín González, Manuel / Nagore, Eduardo / Gómez-Fernández, Cristina / Avilés-Izquierdo, Jose Antonio / Maldonado-Seral, Cayetana / Soriano, Virtudes / Majem-Tarruella, Margarita / Palomar, Virginia / Maseda, Rocio / Martín-Carnicero, Alfonso / Puertolas, Teresa / Godoy, Elena / Cerezuela, Pablo / Ochoa de Olza, Maria / Campos, Begoña / Perez-Ruiz, Elisabeth / Soria, Ainara / Gil-Arnaiz, Irene / Gonzalez-Cao, Maria / Galvez, Elisa / Arance, Ana / Belon, Joaquin / de la Cruz-Merino, Luis / Martín-Algarra, Salvador / Anonymous731066. ·Servicio de Oncología Médica, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain. · Servicio de Dermatología, Hospital Ramón y Cajal, Madrid, Spain. · Servicio de Dermatología, Instituto Valenciano de Oncología, Valencia, Spain. · Servicio de Dermatología, Hospital La Paz, Madrid, Spain. · Servicio de Dermatología, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain. · Servicio de Deramtología, Hospital Universitario Central de Asturias, Oviedo, Spain. · Servicio de Oncología Médica, Instituto Valenciano de Oncología, Valencia, Spain. · Servicio de Oncología Médcica, Hospital de Sant Pau, Barcelona, Spain. · Servicio de Oncología Médica, Hospital General de Valencia, Valencia, Spain. · Servicio de Oncología Médica, Hospital de San Pedro, Logroño, Spain. · Servicio de Oncología, Hospital Universitario Miguel Servet, Zaragoza, Spain. · Servicio de Dermatología, Hospital de Cabueñes, Gijon, Spain. · Servicio de Oncología Médica, Hospital General Universitario Santa Lucia, Cartagena, Spain. · Servicio de Oncología Médica, Instituto Catalan de Oncología, Hospitalet, Spain. · Servicio de Oncología Médica, Hospital Lucus Augusti, Lugo, Spain. · Servicio de Oncología Médica, Hospital Costa del Sol, Marbella, Spain. · Servicio de Oncología Médica, Hospital Ramón y Cajal, Madrid, Spain. · Servicio de Oncología Medica, Hospital Reina Sofía, Tudela, Spain. · Servico de Oncología Médica, Instituto Dexeus, Barcelona, Spain. · Servicio de Oncología Médica, Hospital de Elda, Alicante, Spain. · Servicio de Oncología Medica, Hospital Clinic, Barcelona, Spain. · Servicio de Oncología Médica, Clínica Oncogranada, Granada, Spain. · Servicio de Oncología Médica, Hospital Virgen de la Macarena, Sevilla, Spain. · Departamento de Oncología, Clínica Universidad de Navarra, Pamplona, Spain. ·PLoS One · Pubmed #25874698.

ABSTRACT: INTRODUCTION: Familial history of melanoma is a well-known risk factor for the disease, and 7% melanoma patients were reported to have a family history of melanoma. Data relating to the frequency and clinical and pathological characteristics of both familial and non-familial melanoma in Spain have been published, but these only include patients from specific areas of Spain and do not represent the data for the whole of Spain. PATIENTS AND METHODS: An observational study conducted by the Spanish Group of Melanoma (GEM) analyzed the family history of patients diagnosed with melanoma between 2011 and 2013 in the dermatology and oncology departments. RESULTS: In all, 1047 patients were analyzed, and 69 (6.6%) fulfilled criteria for classical familial melanoma (two or more first-degree relatives diagnosed with melanoma). Taking into account other risk factors for familial melanoma, such as multiple melanoma, pancreatic cancer in the family or second-degree relatives with melanoma, the number of patients fulfilling the criteria increased to 165 (15.8%). Using a univariate analysis, we determined that a Breslow index of less than 1 mm, negative mitosis, multiple melanoma, and a history of sunburns in childhood were more frequent in familial melanoma patients, but a multivariate analysis revealed no differences in any pathological or clinical factor between the two groups. CONCLUSIONS: Similar to that observed in other countries, familial melanoma accounts for 6.6% of melanoma diagnoses in Spain. Although no differences in the multivariate analysis were found, some better prognosis factors, such as Breslow index, seem more frequent in familial melanoma, which reflect a better early detection marker and/or a different biological behavior.