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Melanoma: HELP
Articles by Iván Márquez Rodas
Based on 21 articles published since 2009
(Why 21 articles?)
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Between 2009 and 2019, I. Marquez-Rodas wrote the following 21 articles about Melanoma.
 
+ Citations + Abstracts
1 Guideline SEOM clinical guideline for the management of malignant melanoma (2017). 2018

Berrocal, A / Arance, A / Castellon, V E / de la Cruz, L / Espinosa, E / Cao, M G / Larriba, J L G / Márquez-Rodas, I / Soria, A / Algarra, S M. ·Servicio de Oncología Médica, Consorcio Hospital General Universitario de Valencia, Avda. Tres Cruces 2, 46014, Valencia, Spain. berrocal.alf@gmail.com. · Hospital Clinic I Provincial de Barcelona, Barcelona, Spain. · Hospital Torrecárdenas, Almería, Spain. · Complejo Hospitalario Regional Virgen Macaren, Seville, Spain. · Hospital Universitario la Paz, Madrid, Spain. · Hospital Universitario Quirón Dexeus, Barcelona, Spain. · Hospital Universitario Clínico San Carlos, Madrid, Spain. · Hospital General Universitario Gregorio Marañón, Madrid, Spain. · Hospital Universitario Ramón y Cajal, Madrid, Spain. · Clínica Universitaria de Navarra, Pamplona, Spain. ·Clin Transl Oncol · Pubmed #29116432.

ABSTRACT: All melanoma suspected patients must be confirmed histologically and resected. Sentinel node biopsy must be done when tumor is over 1 mm or if less with high-risk factors. Adjuvant therapy with interferon could be offered for patients with high-risk melanoma and in selected cases radiotherapy can be added. Metastatic melanoma treatment is guided by mutational BRAF status. BRAF wild type patients must receive anti-PD1 containing therapy and BRAF mutated patients BRAF/MEK inhibitors or anti-PD1 containing therapy. Up to 10 years follow up is reasonable for melanoma patients with dermatologic examinations and physical exams.

2 Review A new era in the treatment of melanoma: from biology to clinical practice. 2011

Márquez-Rodas, I / Martín Algarra, S / Avilés Izquierdo, J A / Custodio Cabello, S / Martín, M. ·Servicio de Oncología Médica, Hospital General Universitario Gregorio Marañón, Universidad Complutense, Madrid, Spain. ivanpantic@hotmail.com ·Clin Transl Oncol · Pubmed #22082642.

ABSTRACT: Melanoma is the deadliest cutaneous malignancy and its incidence continues to grow. Until 2011, the treatment options for metastatic melanoma were scarce and without any overall survival benefit. The emergence of new targeted therapies for BRAF mutant melanoma (vemurafenib) and immunotherapy (ipilimumab) has changed the standard of care for this disease. The objective of the present review is to summarise the biological background of the new therapeutic approaches in melanoma, focusing on apoptosis resistance, immune modulation and angiogenesis, and the direct translation into clinical practice.

3 Clinical Trial Nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4-year outcomes of a multicentre, randomised, phase 3 trial. 2018

Hodi, Frank Stephen / Chiarion-Sileni, Vanna / Gonzalez, Rene / Grob, Jean-Jacques / Rutkowski, Piotr / Cowey, Charles Lance / Lao, Christopher D / Schadendorf, Dirk / Wagstaff, John / Dummer, Reinhard / Ferrucci, Pier Francesco / Smylie, Michael / Hill, Andrew / Hogg, David / Marquez-Rodas, Ivan / Jiang, Joel / Rizzo, Jasmine / Larkin, James / Wolchok, Jedd D. ·Dana-Farber Cancer Institute, Boston, MA, USA. Electronic address: stephen_hodi@dfci.harvard.edu. · Veneto Institute of Oncology IOV-IRCCS, Padua, Italy. · University of Colorado Cancer Center, Denver, CO, USA. · Aix-Marseille University and APHM Hospital CHU Timone, Marseille, France. · Maria Skłodowska-Curie Institute - Oncology Centre, Warsaw, Poland. · Texas Oncology-Baylor Charles A Sammons Cancer Center, Dallas, TX, USA. · Department of Oncology, University of Michigan, Ann Arbor, MI, USA. · Department of Dermatology, University of Essen, Essen, Germany; German Cancer Consortium, Heidelberg, Germany. · The College of Medicine, Swansea University, Swansea, UK. · Department of Dermatology, Universitäts Spital, Zürich, Switzerland. · European Institute of Oncology, Milan, Italy. · Cross Cancer Institute, Edmonton, AB, Canada. · Tasman Oncology Research, Southport, QLD, Australia. · Princess Margaret Cancer Centre, Toronto, ON, Canada. · General University Hospital Gregorio Marañón, Madrid, Spain. · Bristol-Myers Squibb, Princeton, NJ, USA. · The Royal Marsden NHS Foundation Trust, London, UK. · Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Cornell Medical College, New York, NY, USA. ·Lancet Oncol · Pubmed #30361170.

ABSTRACT: BACKGROUND: Previously reported results from the phase 3 CheckMate 067 trial showed a significant improvement in objective responses, progression-free survival, and overall survival with nivolumab plus ipilimumab or nivolumab alone compared with ipilimumab alone in patients with advanced melanoma. The aim of this report is to provide 4-year updated efficacy and safety data from this study. METHODS: In this phase 3 trial, eligible patients were aged 18 years or older with previously untreated, unresectable, stage III or stage IV melanoma, known BRAF FINDINGS: Between July 3, 2013, and March 31, 2014, 945 patients were enrolled and randomly assigned to nivolumab plus ipilimumab (n=314), nivolumab (n=316), or ipilimumab (n=315). Median follow-up was 46·9 months (IQR 10·9-51·8) in the nivolumab plus ipilimumab group, 36·0 months (10·5-51·4) in the nivolumab group, and 18·6 months (7·6-49·5) in the ipilimumab group. At a minimum follow-up of 48 months from the date that the final patient was enrolled and randomised, median overall survival was not reached (95% CI 38·2-not reached) in the nivolumab plus ipilimumab group, 36·9 months (28·3-not reached) in the nivolumab group, and 19·9 months (16·9-24·6) in the ipilimumab group. The hazard ratio for death for the combination versus ipilimumab was 0·54 (95% CI 0·44-0·67; p<0·0001) and for nivolumab versus ipilimumab was 0·65 (0·53-0·79; p<0·0001). Median progression-free survival was 11·5 months (95% CI 8·7-19·3) in the nivolumab plus ipilimumab group, 6·9 months (5·1-10·2) in the nivolumab group, and 2·9 months (2·8-3·2) in the ipilimumab group. The hazard ratio for progression-free survival for the combination versus ipilimumab was 0·42 (95% CI 0·35-0·51; p<0·0001) and for nivolumab versus ipilimumab was 0·53 (0·44-0·64; p<0·0001). Treatment-related grade 3-4 adverse events were reported in 185 (59%) of 313 patients who received nivolumab plus ipilimumab, 70 (22%) of 313 who received nivolumab, and 86 (28%) of 311 who received ipilimumab. The most common treatment-related grade 3 adverse events were diarrhoea in the nivolumab plus ipilimumab group (29 [9%] of 313) and in the nivolumab group (nine [3%] of 313) and colitis in the ipilimumab group (23 [7%] of 311); the most common grade 4 adverse event in all three groups was increased lipase (15 [5%] of 313 in the combination group, ten [3%] of 313 in the nivolumab group, and four [1%] of 311 in the ipilimumab group). Serious adverse events were not analysed for the 4-year follow-up. In total for the study, there were four treatment-related deaths: two in the nivolumab plus ipilimumab group (one cardiomyopathy and one liver necrosis), one in the nivolumab group (neutropenia), and one in the ipilimumab group (colon perforation). No additional treatment-related deaths have occurred since the previous (3-year) analysis. INTERPRETATION: The results of this analysis at 4 years of follow-up show that a durable, sustained survival benefit can be achieved with first-line nivolumab plus ipilimumab or nivolumab alone in patients with advanced melanoma. FUNDING: Bristol-Myers Squibb.

4 Clinical Trial Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma. 2017

Weber, Jeffrey / Mandala, Mario / Del Vecchio, Michele / Gogas, Helen J / Arance, Ana M / Cowey, C Lance / Dalle, Stéphane / Schenker, Michael / Chiarion-Sileni, Vanna / Marquez-Rodas, Ivan / Grob, Jean-Jacques / Butler, Marcus O / Middleton, Mark R / Maio, Michele / Atkinson, Victoria / Queirolo, Paola / Gonzalez, Rene / Kudchadkar, Ragini R / Smylie, Michael / Meyer, Nicolas / Mortier, Laurent / Atkins, Michael B / Long, Georgina V / Bhatia, Shailender / Lebbé, Celeste / Rutkowski, Piotr / Yokota, Kenji / Yamazaki, Naoya / Kim, Tae M / de Pril, Veerle / Sabater, Javier / Qureshi, Anila / Larkin, James / Ascierto, Paolo A / Anonymous7111184. ·From New York University Perlmutter Cancer Center, New York (J.W.) · Papa Giovanni XXIII Cancer Center Hospital, Bergamo (M. Mandala), Medical Oncology, National Cancer Institute, Milan (M.D.V.), Oncology Institute of Veneto Istituti di Ricovero e Cura a Carattere Scientifico, Padua (V.C.-S.), Center for Immuno-Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena (M. Maio), Ospedale Policlinico San Martino, Genoa (P.Q.), and Istituto Nazionale Tumori Fondazione Pascale, Naples (P.A.A.) - all in Italy · National and Kapodistrian University of Athens, Athens (H.J.G.) · Hospital Clinic de Barcelona, Barcelona (A.M.A.), and General University Hospital Gregorio Marañón, Madrid (I.M.-R.) - both in Spain · Texas Oncology-Baylor Cancer Center, Dallas (C.L.C.) · Hospices Civils de Lyon, Pierre Bénite (S.D.), Aix-Marseille University, Hospital de la Timone, Marseille (J.-J.G.), Institut Universitaire du Cancer de Toulouse and Centre Hospitalier Universitaire (CHU), Toulouse (N.M.), Université Lille, INSERM Unité 1189, CHU Lille, Lille (L.M.), and Assistance Publique-Hôpitaux de Paris, Dermatology and Centres d'Investigation Clinique, INSERM Unité 976, Hôpital Saint Louis, Université Paris Diderot, Paris (C.L.) - all in France · Oncology Center Sf. Nectarie, Craiova, Romania (M. Schenker) · Princess Margaret Cancer Centre, University of Toronto, Toronto (M.O.B.), and Cross Cancer Institute, Edmonton, AB (M. Smylie) - both in Canada · the Department of Oncology, University of Oxford, Oxford (M.R.M.), and Royal Marsden NHS Foundation Trust, London (J.L.) - both in the United Kingdom · Gallipoli Medical Research Foundation and University of Queensland, Queensland, VIC (V.A.), and Melanoma Institute Australia, University of Sydney, and Royal North Shore and Mater Hospitals, Sydney (G.V.L.) - all in Australia · University of Colorado, Denver (R.G.) · Winship Cancer Institute, Emory University School of Medicine, Atlanta (R.R.K.) · Georgetown-Lombardi Comprehensive Cancer Center, Washington DC (M.B.A.) · University of Washington, Seattle (S.B.) · Maria Sklodowska-Curie Institute-Oncology Center, Warsaw, Poland (P.R.) · Nagoya University Graduate School of Medicine, Nagoya (K.Y.), and the National Cancer Center Hospital, Tokyo (N.Y.) - both in Japan · Seoul National University Hospital, Seoul, South Korea (T.M.K.) · and Bristol-Myers Squibb, Princeton, NJ (V.P, J.S., A.Q.). ·N Engl J Med · Pubmed #28891423.

ABSTRACT: BACKGROUND: Nivolumab and ipilimumab are immune checkpoint inhibitors that have been approved for the treatment of advanced melanoma. In the United States, ipilimumab has also been approved as adjuvant therapy for melanoma on the basis of recurrence-free and overall survival rates that were higher than those with placebo in a phase 3 trial. We wanted to determine the efficacy of nivolumab versus ipilimumab for adjuvant therapy in patients with resected advanced melanoma. METHODS: In this randomized, double-blind, phase 3 trial, we randomly assigned 906 patients (≥15 years of age) who were undergoing complete resection of stage IIIB, IIIC, or IV melanoma to receive an intravenous infusion of either nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks (453 patients) or ipilimumab at a dose of 10 mg per kilogram every 3 weeks for four doses and then every 12 weeks (453 patients). The patients were treated for a period of up to 1 year or until disease recurrence, a report of unacceptable toxic effects, or withdrawal of consent. The primary end point was recurrence-free survival in the intention-to-treat population. RESULTS: At a minimum follow-up of 18 months, the 12-month rate of recurrence-free survival was 70.5% (95% confidence interval [CI], 66.1 to 74.5) in the nivolumab group and 60.8% (95% CI, 56.0 to 65.2) in the ipilimumab group (hazard ratio for disease recurrence or death, 0.65; 97.56% CI, 0.51 to 0.83; P<0.001). Treatment-related grade 3 or 4 adverse events were reported in 14.4% of the patients in the nivolumab group and in 45.9% of those in the ipilimumab group; treatment was discontinued because of any adverse event in 9.7% and 42.6% of the patients, respectively. Two deaths (0.4%) related to toxic effects were reported in the ipilimumab group more than 100 days after treatment. CONCLUSIONS: Among patients undergoing resection of stage IIIB, IIIC, or IV melanoma, adjuvant therapy with nivolumab resulted in significantly longer recurrence-free survival and a lower rate of grade 3 or 4 adverse events than adjuvant therapy with ipilimumab. (Funded by Bristol-Myers Squibb and Ono Pharmaceutical; CheckMate 238 ClinicalTrials.gov number, NCT02388906 ; Eudra-CT number, 2014-002351-26 .).

5 Clinical Trial Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. 2017

Wolchok, Jedd D / Chiarion-Sileni, Vanna / Gonzalez, Rene / Rutkowski, Piotr / Grob, Jean-Jacques / Cowey, C Lance / Lao, Christopher D / Wagstaff, John / Schadendorf, Dirk / Ferrucci, Pier F / Smylie, Michael / Dummer, Reinhard / Hill, Andrew / Hogg, David / Haanen, John / Carlino, Matteo S / Bechter, Oliver / Maio, Michele / Marquez-Rodas, Ivan / Guidoboni, Massimo / McArthur, Grant / Lebbé, Celeste / Ascierto, Paolo A / Long, Georgina V / Cebon, Jonathan / Sosman, Jeffrey / Postow, Michael A / Callahan, Margaret K / Walker, Dana / Rollin, Linda / Bhore, Rafia / Hodi, F Stephen / Larkin, James. ·From the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (J.D.W., M.A.P., M.K.C.) · Oncology Institute of Veneto Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua (V.C.-S.), European Institute of Oncology, Milan (P.F.F.), Center for Immuno-Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena (M.M.), the Immunotherapy and Somatic Cell Therapy Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (M.G.), and Istituto Nazionale Tumori Fondazione Pascale, Naples (P.A.A.) - all in Italy · University of Colorado, Denver (R.G.) · Maria Sklodowska-Curie Institute-Oncology Center, Warsaw, Poland (P.R.) · Aix-Marseille University, Hôpital de la Timone, Marseille (J.-J.G.), and Assistance Publique-Hôpitaux de Paris, Dermatology and Centres d'Investigation Clinique, INSERM Unité 976, Hôpital Saint-Louis, Université Paris Diderot, Paris (C.L.) - both in France · Texas Oncology-Baylor Cancer Center, Dallas (C.L.C.) · University of Michigan, Ann Arbor (C.D.L.) · the College of Medicine, Swansea University, Swansea (J.W.), and Royal Marsden NHS Foundation Trust, London (J.L.) - both in the United Kingdom · the Department of Dermatology, University of Essen, Essen, and the German Cancer Consortium, Heidelberg - both in Germany (D.S.) · Cross Cancer Institute, Edmonton, AB (M.S.), and Princess Margaret Cancer Centre, Toronto (D.H.) - both in Canada · Universitäts Spital, Zurich, Switzerland (R.D.) · Tasman Oncology Research, Southport Gold Coast, QLD (A.H.), Crown Princess Mary Cancer Centre, Melanoma Institute Australia, University of Sydney (M.S.C.), and Melanoma Institute Australia, University of Sydney, and Royal North Shore and Mater Hospitals (G.V.L.), Sydney, and Peter MacCallum Cancer Centre (G.M.) and the Olivia Newton-John Cancer Research Institute, University of Melbourne (J.C.), Melbourne, VIC - all in Australia · Netherlands Cancer Institute, Amsterdam (J.H.) · University Hospitals Leuven, KU Leuven, Leuven, Belgium (O.B.) · General University Hospital Gregorio Marañón, Madrid (I.M.-R.) · Northwestern University, Chicago (J.S.) · Bristol-Myers Squibb, Princeton, NJ (D.W., L.R., R.B.) · and the Dana-Farber Cancer Institute, Boston (F.S.H.). ·N Engl J Med · Pubmed #28889792.

ABSTRACT: BACKGROUND: Nivolumab combined with ipilimumab resulted in longer progression-free survival and a higher objective response rate than ipilimumab alone in a phase 3 trial involving patients with advanced melanoma. We now report 3-year overall survival outcomes in this trial. METHODS: We randomly assigned, in a 1:1:1 ratio, patients with previously untreated advanced melanoma to receive nivolumab at a dose of 1 mg per kilogram of body weight plus ipilimumab at a dose of 3 mg per kilogram every 3 weeks for four doses, followed by nivolumab at a dose of 3 mg per kilogram every 2 weeks; nivolumab at a dose of 3 mg per kilogram every 2 weeks plus placebo; or ipilimumab at a dose of 3 mg per kilogram every 3 weeks for four doses plus placebo, until progression, the occurrence of unacceptable toxic effects, or withdrawal of consent. Randomization was stratified according to programmed death ligand 1 (PD-L1) status, BRAF mutation status, and metastasis stage. The two primary end points were progression-free survival and overall survival in the nivolumab-plus-ipilimumab group and in the nivolumab group versus the ipilimumab group. RESULTS: At a minimum follow-up of 36 months, the median overall survival had not been reached in the nivolumab-plus-ipilimumab group and was 37.6 months in the nivolumab group, as compared with 19.9 months in the ipilimumab group (hazard ratio for death with nivolumab plus ipilimumab vs. ipilimumab, 0.55 [P<0.001]; hazard ratio for death with nivolumab vs. ipilimumab, 0.65 [P<0.001]). The overall survival rate at 3 years was 58% in the nivolumab-plus-ipilimumab group and 52% in the nivolumab group, as compared with 34% in the ipilimumab group. The safety profile was unchanged from the initial report. Treatment-related adverse events of grade 3 or 4 occurred in 59% of the patients in the nivolumab-plus-ipilimumab group, in 21% of those in the nivolumab group, and in 28% of those in the ipilimumab group. CONCLUSIONS: Among patients with advanced melanoma, significantly longer overall survival occurred with combination therapy with nivolumab plus ipilimumab or with nivolumab alone than with ipilimumab alone. (Funded by Bristol-Myers Squibb and others; CheckMate 067 ClinicalTrials.gov number, NCT01844505 .).

6 Clinical Trial Dabrafenib plus trametinib in patients with BRAF 2017

Davies, Michael A / Saiag, Philippe / Robert, Caroline / Grob, Jean-Jacques / Flaherty, Keith T / Arance, Ana / Chiarion-Sileni, Vanna / Thomas, Luc / Lesimple, Thierry / Mortier, Laurent / Moschos, Stergios J / Hogg, David / Márquez-Rodas, Iván / Del Vecchio, Michele / Lebbé, Céleste / Meyer, Nicolas / Zhang, Ying / Huang, Yingjie / Mookerjee, Bijoyesh / Long, Georgina V. ·Melanoma Medical Oncology and Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: mdavies@mdanderson.org. · Service de Dermatologie Générale et Oncologique, Hôpital A Paré, Assistance Publique-Hôpitaux de Paris, Boulogne Billancourt, France; EA 4340, Université Versailles Saint-Quentin-en-Yvelines, Boulogne Billancourt, France. · Gustave Roussy, Département de Médecine Oncologique, Service de Dermatologie et Université Paris-Sud, Faculté de Médecine, Villejuif, France. · Service de Dermatologie, Centre Hospitalo-Universitaire Timone, Aix Marseille University, Marseille, France. · Developmental Therapeutics and Melanoma Programs, Massachusetts General Hospital Cancer Center, Boston, MA, USA. · Department of Medical Oncology, Hospital Clinic of Barcelona, Carrer de Villarroel, Barcelona, Spain. · Melanoma and Oesophageal Oncology Unit, Veneto Oncology Institute-IRCCS, Padova, Italy. · Service de Dermatologie, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France. · Oncologie Dermatologique, Centre Eugène Marquis, Rennes, France. · Clinique de Dermatologie, Unité d'Onco-Dermatologie, Le Centre Hospitalier Régional Universitaire de Lille, University Lille 2, Lille, France. · Melanoma Program, Medical Oncology, UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA. · Clinical Cancer Research Unit, Princess Margaret Cancer Centre, Toronto, ON, Canada. · Servicio de Oncología Médica; Hospital General Universitario Gregorio Marañon, Madrid, Spain. · Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. · APHP Dermatology and CIC Departments, INSERM U976, University Paris Diderot, Hôpital Saint Louis Paris, Paris, France. · Medical Oncology, Institut Universitaire du Cancer Toulouse Oncopole, Toulouse, France. · Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. · Melanoma Institute Australia, The University of Sydney, Royal North Shore and Mater Hospitals, Sydney, NSW, Australia. ·Lancet Oncol · Pubmed #28592387.

ABSTRACT: BACKGROUND: Dabrafenib plus trametinib improves clinical outcomes in BRAF METHODS: This ongoing, multicentre, multicohort, open-label, phase 2 study evaluated oral dabrafenib (150 mg twice per day) plus oral trametinib (2 mg once per day) in four patient cohorts with melanoma brain metastases enrolled from 32 hospitals and institutions in Europe, North America, and Australia: (A) BRAF FINDINGS: Between Feb 28, 2014, and Aug 5, 2016, 125 patients were enrolled in the study: 76 patients in cohort A; 16 patients in cohort B; 16 patients in cohort C; and 17 patients in cohort D. At the data cutoff (Nov 28, 2016) after a median follow-up of 8·5 months (IQR 5·5-14·0), 44 (58%; 95% CI 46-69) of 76 patients in cohort A achieved an intracranial response. Intracranial response by investigator assessment was also achieved in nine (56%; 95% CI 30-80) of 16 patients in cohort B, seven (44%; 20-70) of 16 patients in cohort C, and ten (59%; 33-82) of 17 patients in cohort D. The most common serious adverse events related to study treatment were pyrexia for dabrafenib (eight [6%] of 125 patients) and decreased ejection fraction (five [4%]) for trametinib. The most common grade 3 or worse adverse events, regardless of study drug relationship, were pyrexia (four [3%] of 125) and headache (three [2%]). INTERPRETATION: Dabrafenib plus trametinib was active with a manageable safety profile in this melanoma population that was consistent with previous dabrafenib plus trametinib studies in patients with BRAF FUNDING: Novartis.

7 Clinical Trial Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. 2015

Larkin, James / Chiarion-Sileni, Vanna / Gonzalez, Rene / Grob, Jean Jacques / Cowey, C Lance / Lao, Christopher D / Schadendorf, Dirk / Dummer, Reinhard / Smylie, Michael / Rutkowski, Piotr / Ferrucci, Pier F / Hill, Andrew / Wagstaff, John / Carlino, Matteo S / Haanen, John B / Maio, Michele / Marquez-Rodas, Ivan / McArthur, Grant A / Ascierto, Paolo A / Long, Georgina V / Callahan, Margaret K / Postow, Michael A / Grossmann, Kenneth / Sznol, Mario / Dreno, Brigitte / Bastholt, Lars / Yang, Arvin / Rollin, Linda M / Horak, Christine / Hodi, F Stephen / Wolchok, Jedd D. ·From the Department of Medical Oncology, Royal Marsden Hospital, London (J.L.), and South West Wales Cancer Institute, Singleton Hospital, Swansea (J.W.) - both in the United Kingdom · Melanoma Oncology Unit, Veneto Region Oncology Research Institute, Padua (V.C.-S.), Oncology of Melanoma Unit, European Institute of Oncology, Milan (P.F.F.), University Hospital of Siena, Siena (M.M.), and Istituto Nazionale Tumori Fondazione Pascale, Naples (P.A.A.) - all in Italy · Division of Medical Oncology, University of Colorado, Denver, Denver (R.G.) · Aix-Marseille University, Hôpital de La Timone, Assitance Publique-Hôpitaux de Marseille, Marseille (J.J.G.), and Hôtel Dieu Place Alexis Ricordeau, Nantes (B.D.) - both in France · Baylor Charles A. Sammons Cancer Center, Dallas (C.L.C.) · Departments of Internal Medicine and Dermatology, University of Michigan, Ann Arbor (C.D.L.) · Department of Dermatology, University of Essen, Essen, Germany (D.S.) · University of Zürich Hospital, Zurich, Switzerland (R.D.) · Cross Cancer Institute, Edmonton, AB, Canada (M. Smylie) · Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (P.R.) · Tasman Oncology Research, Southport Gold Coast, QLD (A.H.), and Westmead and Blacktown Hospitals (M.S.C.) and Melanoma Institute Australia (M.S.C., G.V.L.), University of Sydney, and the Mater Hospital (G.V.L.), Sydney, and Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, VIC (G.A.M.) - all in Australia · Division of Medical Oncology, the Netherlands Cancer Institute, Amsterdam (J.B.H.) · Servicio de Oncología Médica, Hospital General Universitario Gregorio Marañón, Madrid (I.M.-R.) · Ludwig Center, Memorial Sloan Kettering Cancer Center (M.K.C., M.A.P., J.D.W.) and Weill Cornell Medical College (M.K.C., M.A.P., J.D.W.) - both in New York · Huntsman Cancer Institute, University of Utah, Salt Lake City (K.G.) · Yale Cancer Center, Smilow Cancer Hospital of the Yale-New Haven Hospital, Yale University Sc ·N Engl J Med · Pubmed #26027431.

ABSTRACT: BACKGROUND: Nivolumab (a programmed death 1 [PD-1] checkpoint inhibitor) and ipilimumab (a cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4] checkpoint inhibitor) have been shown to have complementary activity in metastatic melanoma. In this randomized, double-blind, phase 3 study, nivolumab alone or nivolumab plus ipilimumab was compared with ipilimumab alone in patients with metastatic melanoma. METHODS: We assigned, in a 1:1:1 ratio, 945 previously untreated patients with unresectable stage III or IV melanoma to nivolumab alone, nivolumab plus ipilimumab, or ipilimumab alone. Progression-free survival and overall survival were coprimary end points. Results regarding progression-free survival are presented here. RESULTS: The median progression-free survival was 11.5 months (95% confidence interval [CI], 8.9 to 16.7) with nivolumab plus ipilimumab, as compared with 2.9 months (95% CI, 2.8 to 3.4) with ipilimumab (hazard ratio for death or disease progression, 0.42; 99.5% CI, 0.31 to 0.57; P<0.001), and 6.9 months (95% CI, 4.3 to 9.5) with nivolumab (hazard ratio for the comparison with ipilimumab, 0.57; 99.5% CI, 0.43 to 0.76; P<0.001). In patients with tumors positive for the PD-1 ligand (PD-L1), the median progression-free survival was 14.0 months in the nivolumab-plus-ipilimumab group and in the nivolumab group, but in patients with PD-L1-negative tumors, progression-free survival was longer with the combination therapy than with nivolumab alone (11.2 months [95% CI, 8.0 to not reached] vs. 5.3 months [95% CI, 2.8 to 7.1]). Treatment-related adverse events of grade 3 or 4 occurred in 16.3% of the patients in the nivolumab group, 55.0% of those in the nivolumab-plus-ipilimumab group, and 27.3% of those in the ipilimumab group. CONCLUSIONS: Among previously untreated patients with metastatic melanoma, nivolumab alone or combined with ipilimumab resulted in significantly longer progression-free survival than ipilimumab alone. In patients with PD-L1-negative tumors, the combination of PD-1 and CTLA-4 blockade was more effective than either agent alone. (Funded by Bristol-Myers Squibb; CheckMate 067 ClinicalTrials.gov number, NCT01844505.).

8 Article Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. 2019

Larkin, James / Chiarion-Sileni, Vanna / Gonzalez, Rene / Grob, Jean-Jacques / Rutkowski, Piotr / Lao, Christopher D / Cowey, C Lance / Schadendorf, Dirk / Wagstaff, John / Dummer, Reinhard / Ferrucci, Pier F / Smylie, Michael / Hogg, David / Hill, Andrew / Márquez-Rodas, Ivan / Haanen, John / Guidoboni, Massimo / Maio, Michele / Schöffski, Patrick / Carlino, Matteo S / Lebbé, Céleste / McArthur, Grant / Ascierto, Paolo A / Daniels, Gregory A / Long, Georgina V / Bastholt, Lars / Rizzo, Jasmine I / Balogh, Agnes / Moshyk, Andriy / Hodi, F Stephen / Wolchok, Jedd D. ·From the Royal Marsden NHS Foundation Trust, London (J.L.), and the College of Medicine, Swansea University, Swansea (J.W.) - both in the United Kingdom · the Oncology Institute of Veneto IRCCS, Padua (V.C.-S.), the European Institute of Oncology, IRCCS, Milan (P.F.F.), Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples (P.A.A.), the Immunotherapy and Somatic Cell Therapy Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (M.G.), and the Center for Immuno-Oncology, Medical Oncology and Immunotherapy, University Hospital, Siena (M.M.) - all in Italy · the University of Colorado Cancer Center, Aurora (R.G.) · Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille Hôpital Timone, Marseille (J.-J.G.), and Université de Paris, INSERM Unité 976, Assistance Publique-Hôpitaux de Paris Dermatology and Centres d'Investigation Clinique, Saint Louis Hospital, Paris (C.L.) - both in France · the Maria Sklodowska-Curie Institute-Oncology Center, Warsaw, Poland (P.R.) · the University of Michigan, Ann Arbor (C.D.L.) · Texas Oncology-Baylor Charles A. Sammons Cancer Center, Dallas (C.L.C.) · the Department of Dermatology, University of Essen, Essen, and the German Cancer Consortium, Heidelberg - both in Germany (D.S.) · Universitäts Spital, Zurich, Switzerland (R.D.) · Cross Cancer Institute, Edmonton, AB (M.S.), and the Princess Margaret Cancer Centre, Toronto (D.H.) - both in Canada · Tasman Oncology Research, Southport, QLD (A.H.), the Crown Princess Mary Cancer Centre, Melanoma Institute Australia, University of Sydney, Sydney, NSW (M.S.C., G.V.L.), and the Royal North Shore and Mater Hospitals (G.V.L.), Sydney, and the Peter MacCallum Cancer Centre, Melbourne, VIC (G.M.) - all in Australia · General University Hospital Gregorio Marañon and Centro de Investigación Biomédica en Red de Oncología, Madrid (I.M.-R.) · the Netherlands Cancer Institute, Amsterdam (J.H.) · the Leuven Cancer Institute, Department of General Medical Oncology, University Hospital Leuven, Leuven, Belgium (P.S.) · University of California San Diego Health-La Jolla Moores Cancer Center, La Jolla (G.A.D.) · the Department of Oncology, Odense University Hospital, Odense, Denmark (L.B.) · Bristol-Myers Squibb, Princeton, NJ (J.I.R., A.B., A.M.) · Dana-Farber Cancer Institute, Boston (F.S.H.) · and the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (J.D.W.). ·N Engl J Med · Pubmed #31562797.

ABSTRACT: BACKGROUND: Nivolumab plus ipilimumab or nivolumab alone resulted in longer progression-free and overall survival than ipilimumab alone in a trial involving patients with advanced melanoma. We now report 5-year outcomes in the trial. METHODS: We randomly assigned patients with previously untreated advanced melanoma to receive one of the following regimens: nivolumab (at a dose of 1 mg per kilogram of body weight) plus ipilimumab (3 mg per kilogram) every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram every 2 weeks); nivolumab (3 mg per kilogram every 2 weeks) plus ipilimumab-matched placebo; or ipilimumab (3 mg per kilogram every 3 weeks for four doses) plus nivolumab-matched placebo. The two primary end points were progression-free survival and overall survival in the nivolumab-plus-ipilimumab group and in the nivolumab group, as compared with the ipilimumab group. RESULTS: At a minimum follow-up of 60 months, the median overall survival was more than 60.0 months (median not reached) in the nivolumab-plus-ipilimumab group and 36.9 months in the nivolumab group, as compared with 19.9 months in the ipilimumab group (hazard ratio for death with nivolumab plus ipilimumab vs. ipilimumab, 0.52; hazard ratio for death with nivolumab vs. ipilimumab, 0.63). Overall survival at 5 years was 52% in the nivolumab-plus-ipilimumab group and 44% in the nivolumab group, as compared with 26% in the ipilimumab group. No sustained deterioration of health-related quality of life was observed during or after treatment with nivolumab plus ipilimumab or with nivolumab alone. No new late toxic effects were noted. CONCLUSIONS: Among patients with advanced melanoma, sustained long-term overall survival at 5 years was observed in a greater percentage of patients who received nivolumab plus ipilimumab or nivolumab alone than in those who received ipilimumab alone, with no apparent loss of quality of life in the patients who received regimens containing nivolumab. (Funded by Bristol-Myers Squibb and others; CheckMate 067 ClinicalTrials.gov number, NCT01844505.).

9 Article The impact of patient characteristics and disease-specific factors on first-line treatment decisions for BRAF-mutated melanoma: results from a European expert panel study. 2018

Ascierto, Paolo A / Bastholt, Lars / Ferrucci, Pier F / Hansson, Johan / Márquez Rodas, Iván / Payne, Miranda / Robert, Caroline / Thomas, Luc / Utikal, Jochen S / Wolter, Pascal / Kudlac, Amber / Tuson, Harriet / McKendrick, Jan. ·Istituto Nazionale Tumori Fondazione G. Pascale, Naples. · Odense University Hospital, Odense, Denmark. · European Institute of Oncology, Milan, Italy. · Karolinska Institutet, Stockholm, Sweden. · Hospital General Universitario Gregorio Marañon, Madrid, Spain. · Oxford University Hospitals NHS Foundation Trust, Oxford. · Gustave-Roussy and Paris-Sud University, Villejuif. · Lyon 1 University, Lyon Cancer Research Center, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France. · German Cancer Research Center (DKFZ) and Heidelberg University, Mannheim, Germany. · CHR Verviers East Belgium, Verviers, Belgium. · PRMA Consulting Ltd, Fleet, UK. ·Melanoma Res · Pubmed #29750751.

ABSTRACT: Treatment decisions for advanced melanoma are increasingly complex and guidelines provide limited advice on how to choose between immunotherapy and targeted therapy for first-line treatment. A Delphi study was carried out to understand which patient characteristics and disease-related factors inform clinicians' choices of first-line treatment for BRAF-mutated melanoma. Twelve European melanoma specialists experienced in using immunotherapies and targeted agents participated in a double-blind two-phase Delphi study. In phase 1, participants completed a questionnaire developed after reviewing patient characteristics and disease-related factors reported in trials, clinical guidelines, and health technology assessments. Phase 2 was an expert panel meeting to explore outstanding issues from phase 1 and seek consensus, defined as 80% agreement. Twenty patient-related and disease-related characteristics were considered. There was consensus that tumor burden (83% of clinicians) and disease tempo (83%) are very or extremely important factors when selecting first-line treatment. Several components were deemed important when assessing tumor burden: brain metastases (82% of clinicians) and location of metastases (89%). There was consensus that disease tempo can be quantified in clinical practice, but not on a formal classification applicable to all patients. Lactate dehydrogenase level is a component of both tumor burden and disease tempo; all clinicians considered lactate dehydrogenase important when choosing first-line treatment. The majority (92%) did not routinely test programmed death ligand-1 status in patients with melanoma. Clinicians agreed that choosing a first-line treatment for advanced melanoma is a complex, multifactorial process and that clinical judgment remains the most important element of decision-making until research can provide clinicians with better scientific parameters and tools for first-line decision-making.

10 Article Dabrafenib plus trametinib for compassionate use in metastatic melanoma: A STROBE-compliant retrospective observational postauthorization study. 2017

Martín Algarra, Salvador / Soriano, Virtudes / Fernández-Morales, Luis / Berciano-Guerrero, Miguel-Ángel / Mujika, Karmele / Manzano, José Luis / Puértolas Hernández, Teresa / Soria, Ainara / Rodríguez-Abreu, Delvys / Espinosa Arranz, Enrique / Medina Martínez, Javier / Márquez-Rodas, Ivan / Rubió-Casadevall, Jordi / Ortega, María Eugenia / Jurado García, José Miguel / Lecumberri Biurrun, María José / Palacio, Isabel / Rodríguez de la Borbolla Artacho, María / Altozano, Javier Pérez / Castellón Rubio, Victoria Eugenia / García, Almudena / Luna, Pablo / Ballesteros, Anabel / Fernández, Ovidio / López Martín, Jose Antonio / Berrocal, Alfonso / Arance, Ana. ·Medical Oncology, Clínica Universidad de Navarra, Pamplona. · Instituto Valenciano de Oncología, Valencia. · Medical Oncology, Parc Taulí Sabadell Hospital Universitario, Sabadell. · Oncología Intercentros, Hospitales Universitarios Regional y Virgen de la Victoria (HURyVV) and Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga. · Onkologikoa, Instituto Oncológico de Kutxa, San Sebastian. · Instituto Catalán de Oncología, ICO-Badalona, Hospital Germans Trías I Pujol, Barcelona. · Medical Oncology, Hospital Universitario Miguel Servet, Zaragoza. · Medical Oncology, Hospital Universitario Ramón y Cajal, Madrid. · Medical Oncology, Complejo Hospitalario Universitario Insular-Materno Infantil de Gran Canaria, Las Palmas de Gran Canaria. · Medical Oncology, Hospital Universitario La Paz, Madrid. · Medical Oncology, Hospital Virgen de la Salud, Toledo. · Medical Oncology, Hospital General Universitario Gregorio Marañón, Madrid. · Instituto Catalán de Oncología Girona, Girona. · Medical Oncology, Hospital Universitario Arnau de Vilanova, Lleida. · Medical Oncology, Hospital Universitario San Cecilio, Granada. · Medical Oncology, Complejo Hospitalario de Navarra, Pamplona. · Medical Oncology, Hospital Universitario Central de Asturias, Oviedo. · Medical Oncology, Hospital Universitario Nuestra Señora de Valme, Sevilla. · Medical Oncology, Hospital General Universitario de Elche, Alicante. · Medical Oncology, Complejo Hospitalario Torrecárdenas de Almería, Almería. · Medical Oncology, Hospital Marqués de Valdecilla, Santander. · Medical Oncology, Hospital Universitario Son Espases, Palma de Mallorca. · Medical Oncology, Hospital Universitario La Princesa, Madrid. · Medical Oncology, Complejo Hospitalario Universitario Ourense, Ourense. · Medical Oncology, Hospital Universitario 12 de Octubre, Madrid. · Medical Oncology, Hospital General Universitario de Valencia, Valencia. · Medical Oncology, Hospital Clínic Barcelona, Barcelona, Spain. ·Medicine (Baltimore) · Pubmed #29384960.

ABSTRACT: The main objective of the study was to evaluate the efficacy and safety of dabrafenib alone or combined with trametinib for compassionate use in patients with metastatic melanoma.This retrospective, observational study involved 135 patients with unresectable stage IIIC or stage IV melanoma from an expanded-access program at 30 Spanish centers.Forty-eight patients received dabrafenib monotherapy and 87 received combination dabrafenib and trametinib; 4.4% and 95.6% of the patients had stage IIIC and IV melanoma, respectively. All patients showed BRAF mutations in their primary or metastatic lesions; 3 were positive for V600K while the remainder had V600E or V600+. A positive response to treatment was reported in 89.3% of the patients. Overall survival rates at 12 and 24 months were 59.6% (95% confidence interval [CI], 52.5-68.9%) and 36.4% (95% CI, 27.8-45%), respectively. Progression-free survival rates at 12 and 24 months were 39.3% (95% CI, 31.1-47.5%) and 21.6% (95% CI, 14.5-28.7%), respectively. Fifty-seven patients (42.2%) reported cutaneous toxicity of any type, mainly hyperkeratosis (14.8%) and rash (11.9%). The most frequent adverse events were pyrexia (27.4%), asthenia (19.3%), arthralgia (16.9%), and diarrhoea (13.2%).Our results suggest that both dabrafenib alone or in combination with trametinib are effective for compassionate use in terms of response and/or survival rates. However, differences in patients' prognostic features ought to be considered. No new findings were revealed regarding the safety profiles of either regimen. This is the first study to evaluate the efficacy of these 2 selective BRAF and mitogen-activated extracellular signal-regulated kinase inhibitors in a real-world setting in Spain.

11 Article Nivolumab for Patients With Advanced Melanoma Treated Beyond Progression: Analysis of 2 Phase 3 Clinical Trials. 2017

Long, Georgina V / Weber, Jeffrey S / Larkin, James / Atkinson, Victoria / Grob, Jean-Jacques / Schadendorf, Dirk / Dummer, Reinhard / Robert, Caroline / Márquez-Rodas, Ivan / McNeil, Catriona / Schmidt, Henrik / Briscoe, Karen / Baurain, Jean-François / Hodi, F Stephen / Wolchok, Jedd D. ·Melanoma Institute Australia, University of Sydney, Sydney, New South Wales, Australia. · Mater Hospital, North Sydney, New South Wales, Australia. · Department of Medical Oncology, Moffitt Cancer Center, Tampa, Florida. · now with Department of Medical Oncology, Laura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York. · Department of Oncology, Royal Marsden Hospital, London, United Kingdom. · Gallipoli Medical Research Foundation and Princess Alexandra Hospital, and University of Queensland, Queensland, Australia. · Department of Dermatology and Skin Cancer, Hospital Timone APHM, Aix-Marseille University, Marseille, France. · Department of Skin, University Hospital Essen, Essen, Germany. · Department of Urology, University Hospital Essen, Essen, Germany. · Department of Dermatology, UniversitaetsSpital, Zurich, Switzerland. · Department of Medicine Institute Gustave Roussy, Gustave Roussy and Paris-Sud University, Villejuif Paris-Sud, France. · Servicio de Oncología Médica, Hospital General Universitario Gregorio Marañón, Madrid, Spain. · Chris O'Brien Lifehouse, Melanoma Institute Australia, Camperdown, New South Wales, Australia. · Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia. · Department of Oncology, Aarhus University Hospital, Aarhus, Denmark. · Department of Medical Oncology, Coffs Harbour Health Campus, New South Wales, Australia. · Melanoma Clinic at King Albert II Cancer Institute, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Bruxelles, Belgium. · Melanoma Center and Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. · Ludwig Center for Cancer Immunotherapy at Memorial Sloan Kettering Cancer Center, New York, New York. ·JAMA Oncol · Pubmed #28662232.

ABSTRACT: Importance: Immune checkpoint inhibitors have demonstrated atypical response patterns, which may not be fully captured by conventional response criteria. There is a need to better understand the potential benefit of continued immune checkpoint inhibition beyond progression. Objective: To evaluate the safety and potential benefit of nivolumab (anti-programmed cell death receptor 1) monotherapy beyond Response Evaluation Criteria in Solid Tumors (RECIST) v1.1-defined progression. Design, Setting, and Participants: Pooled, retrospective analysis of data from phase 3 trials of nivolumab in treatment-naive patients with advanced melanoma (CheckMate 066 or CheckMate 067) conducted at academic and clinical cancer centers. Participants were patients treated beyond first disease progression, defined as those who received their last dose of nivolumab more than 6 weeks after progression (TBP group); and patients not treated beyond progression, who discontinued nivolumab therapy before or at progression (non-TBP group). Data analyses were conducted from November 6, 2015, to January 11, 2017. Interventions: Nivolumab (3 mg/kg every 2 weeks) administered until progression or unacceptable toxic effects. Patients could be treated beyond progression if deriving apparent clinical benefit and tolerating study drug, at the investigator's discretion. Main Outcomes and Measures: Tumor response and safety in TBP and non-TBP patients. Results: Among 526 randomized patients (39% [n = 203] female; median age, 62 years [range, 18-90 years]), 306 (58%) experienced disease progression, including 85 (28%) TBP patients and 221 (72%) non-TBP patients. Twenty-four (28%) of the TBP patients had a target lesion reduction of greater than 30% after progression compared with baseline (TBP>30% group). At the time of this analysis, 65 (76%) TBP patients and 21 (87%) TBP>30% patients were still alive; 27 (32%) and 11 (46%), respectively, continued to receive treatment. Median (range) time from progression to last dose of treatment was 4.7 (1.4-25.8) months for TBP patients and 7.6 (2.4-19.4) months for TBP>30% patients. Median (range) time from progression to greater than 30% tumor reduction was 1.4 (0.2-7.0) months. Treatment-related select grade 3 to 4 adverse events were similar in the TBP and non-TBP groups (5 [6%] and 9 [4%], respectively). Conclusions and Relevance: A substantial proportion of selected patients treated with frontline nivolumab who were clinically stable and judged to be eligible for treatment beyond RECIST v1.1-defined progression by the treating investigators derived apparent clinical benefit without compromising safety. Further analysis will help define the potential benefit of continued nivolumab treatment beyond progression. Trial Registration: clinicaltrials.gov Identifiers: NCT01721772 (CheckMate 066) and NCT01844505 (CheckMate 067).

12 Article Efficacy and Safety of Nivolumab Alone or in Combination With Ipilimumab in Patients With Mucosal Melanoma: A Pooled Analysis. 2017

D'Angelo, Sandra P / Larkin, James / Sosman, Jeffrey A / Lebbé, Celeste / Brady, Benjamin / Neyns, Bart / Schmidt, Henrik / Hassel, Jessica C / Hodi, F Stephen / Lorigan, Paul / Savage, Kerry J / Miller, Wilson H / Mohr, Peter / Marquez-Rodas, Ivan / Charles, Julie / Kaatz, Martin / Sznol, Mario / Weber, Jeffrey S / Shoushtari, Alexander N / Ruisi, Mary / Jiang, Joel / Wolchok, Jedd D. ·Sandra P. D'Angelo, Alexander N. Shoushtari, and Jedd D. Wolchok, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY · James Larkin, Royal Marsden Hospital, London · Paul Lorigan, University of Manchester, Manchester, United Kingdom · Jeffrey A. Sosman, Vanderbilt University Medical Center, Nashville, TN · Celeste Lebbé, Saint-Louis Hospital, Institut National de la Santé et de la Recherche Médicale U976, Université Paris Diderot, Paris · Julie Charles, Grenoble University Hospital, Grenoble Alps University, Grenoble, France · Benjamin Brady, Cabrini Health, Melbourne, Australia · Bart Neyns, Universitair Ziekenhuis Brussel, Brussels, Belgium · Henrik Schmidt, Århus University, Åarhus, Denmark · Jessica C. Hassel, University Hospital Heidelberg, Heidelberg · Peter Mohr, Elbe Kliniken Buxtehude, Buxtehude · Martin Kaatz, SRH Waldklinikum Gera, University Hospital Jena, Jena, Germany · F. Stephen Hodi, Dana-Farber Cancer Institute, Boston, MA · Kerry J. Savage, BC Cancer Agency, University of British Columbia, Vancouver · Wilson H. Miller Jr, Lady Davis Institute and Jewish General Hospital, McGill University, Montreal, Canada · Ivan Marquez-Rodas, Hospital General Universitario Gregorio Marañón, Madrid, Spain · Mario Sznol, Yale University School of Medicine and Smilow Cancer Center, Yale-New Haven Hospital, New Haven, CT · Jeffrey S. Weber, Moffitt Cancer Center, Tampa, FL · and Mary Ruisi and Joel Jiang, Bristol-Myers Squibb, Princeton, NJ. ·J Clin Oncol · Pubmed #28056206.

ABSTRACT: Purpose Mucosal melanoma is an aggressive malignancy with a poor response to conventional therapies. The efficacy and safety of nivolumab (a programmed death-1 checkpoint inhibitor), alone or combined with ipilimumab (a cytotoxic T-lymphocyte antigen-4 checkpoint inhibitor), have not been reported in this rare melanoma subtype. Patients and Methods Data were pooled from 889 patients who received nivolumab monotherapy in clinical studies, including phase III trials; 86 (10%) had mucosal melanoma and 665 (75%) had cutaneous melanoma. Data were also pooled for patients who received nivolumab combined with ipilimumab (n = 35, mucosal melanoma; n = 326, cutaneous melanoma). Results Among patients who received nivolumab monotherapy, median progression-free survival was 3.0 months (95% CI, 2.2 to 5.4 months) and 6.2 months (95% CI, 5.1 to 7.5 months) for mucosal and cutaneous melanoma, with objective response rates of 23.3% (95% CI, 14.8% to 33.6%) and 40.9% (95% CI, 37.1% to 44.7%), respectively. Median progression-free survival in patients treated with nivolumab combined with ipilimumab was 5.9 months (95% CI, 2.8 months to not reached) and 11.7 months (95% CI, 8.9 to 16.7 months) for mucosal and cutaneous melanoma, with objective response rates of 37.1% (95% CI, 21.5% to 55.1%) and 60.4% (95% CI, 54.9% to 65.8%), respectively. For mucosal and cutaneous melanoma, respectively, the incidence of grade 3 or 4 treatment-related adverse events was 8.1% and 12.5% for nivolumab monotherapy and 40.0% and 54.9% for combination therapy. Conclusion To our knowledge, this is the largest analysis of data for anti-programmed death-1 therapy in mucosal melanoma to date. Nivolumab combined with ipilimumab seemed to have greater efficacy than either agent alone, and although the activity was lower in mucosal melanoma, the safety profile was similar between subtypes.

13 Article Pembrolizumab for advanced melanoma: experience from the Spanish Expanded Access Program. 2017

González-Cao, M / Arance, A / Piulats, J M / Marquez-Rodas, I / Manzano, J L / Berrocal, A / Crespo, G / Rodriguez, D / Perez-Ruiz, E / Berciano, M / Soria, A / Castano, A G / Espinosa, E / Montagut, C / Alonso, L / Puertolas, T / Aguado, C / Royo, M A / Blanco, R / Rodríguez, J F / Muñoz, E / Mut, P / Barron, F / Martin-Algarra, S / Anonymous4770892. ·Translational Cancer Research Unit, Dr. Rosell Oncology Institute, Quiron Dexeus University Hospital, 08028, Barcelona, Spain. mgonzalezcao@oncorosell.com. · Hospital Clinic I Provincial, Barcelona, Spain. · Catalan Institute of Oncology, Barcelona, Spain. · Gregorio Marañón Institute of Health Research, Madrid, Spain. · Germans Trias I Pujol University Hospital, Barcelona, Spain. · General University Hospital, Valencia, Spain. · Burgos University Hospital, Burgos, Spain. · Insular University Hospital of Gran Canaria, Canary Islands, Spain. · Costa del Sol Hospital, Marbella, Malaga, Spain. · Regional University Hospital of Malaga, Malaga, Spain. · Ramony Cajal Hospital, Madrid, Spain. · Marqués de Valdecilla University Hospital, Santander, Spain. · La Paz University Hospital, Madrid, Spain. · Del Mar University Hospital, Barcelona, Spain. · Virgen de la Victoria Hospital, Malaga, Spain. · Miguel Servet University Hospital, Zaragoza, Spain. · San Carlos Hospital, Madrid, Spain. · Dr. Peset Hospital, Valencia, Spain. · Consorci Sanitari de Terrassa, Barcelona, Spain. · Clara Campal Hospital, Madrid, Spain. · Valld'Hebron University Hospital, Barcelona, Spain. · Son Llatzer University Hospital, Mallorca, Spain. · National Cancer Institute, Mexico City, Mexico. · Navarra University Clinic, Pamplona, Spain. ·Clin Transl Oncol · Pubmed #28054320.

ABSTRACT: BACKGROUND: The programmed death (PD-1) inhibitor pembrolizumab has been recently approved for the treatment of advanced melanoma. We evaluated the clinical activity of pembrolizumab in melanoma patients treated under the Spanish Expanded Access Program. METHODS: Advanced melanoma patients who failed to previous treatment lines were treated with pembrolizumab 2 mg/kg every three weeks. Patients with brain metastases were not excluded if they were asymptomatic. Data were retrospectively collected from 21 centers in the Spanish Melanoma Group. RESULTS: Sixty-seven advanced melanoma patients were analyzed. Most patients were stage M1c (73.1%), had high LDH levels (55.2%) and had ECOG PS 1 or higher (59.7%). For cutaneous melanoma patients, median overall survival was 14.0 months; the 18-month overall survival rate was 47.1%. Overall response rate was 27%, including three patients with complete responses (6.5%). Median response duration was not reached, with 83.3% of responses ongoing (3.5 m+ to 20.4 m+). From ten patients included with brain metastases, four (40%) had an objective response, two (20%) of them achieved a complete response. Significant prognostic factors for overall survival were LDH level, ECOG PS and objective response. There were no serious adverse events. CONCLUSION: Although this was a heavily pretreated cohort, pembrolizumab activity at the approved dose and schedule was confirmed in the clinical setting with long-term responders, also including patients with brain metastases.

14 Article Who detects melanoma? Impact of detection patterns on characteristics and prognosis of patients with melanoma. 2016

Avilés-Izquierdo, José Antonio / Molina-López, Irene / Rodríguez-Lomba, Enrique / Marquez-Rodas, Ivan / Suarez-Fernandez, Ricardo / Lazaro-Ochaita, Pablo. ·Department of Dermatology, Hospital General Universitario "Gregorio Marañón," Madrid, Spain. Electronic address: jaavilesizquierdo@gmail.com. · Department of Dermatology, Hospital General Universitario "Gregorio Marañón," Madrid, Spain. · Department of Medical Oncology, Hospital General Universitario "Gregorio Marañón," Madrid, Spain. ·J Am Acad Dermatol · Pubmed #27645105.

ABSTRACT: BACKGROUND: Despite the importance of early diagnosis, patients with cutaneous melanoma often seek consultation at advanced stages of the disease. The impact on prognosis according to who first detects the primary tumor has not been established. OBJECTIVE: This study aims to determine who first detects melanoma, the reasons that patients with melanoma consult a doctor, and the impact of detection patterns on the characteristics and prognosis of melanoma. METHODS: Seven hundred eighty-three patients with cutaneous melanoma who were diagnosed between 1996 and 2012 were included. Associations between who first noticed the melanoma (ie, self-detected, relatives, health care workers, or dermatologists), epidemiology, clinical presentation, histology, and patient outcomes were analyzed. RESULTS: Most melanomas were self-detected (53%). Among these patients, 32% consulted because of bleeding, itching/pain, or nodule enlargement. There were more melanomas self-detected among women than among men, and these had a better prognosis. Men had significantly more melanomas on non-easily visible locations than women did. Among melanomas noticed by dermatologists, 80% were incidental findings. Self-detected melanomas were thicker and more frequently ulcerated, developed metastases more often, and were associated with more melanoma-related deaths. CONCLUSIONS: Patients with melanomas detected by dermatologists had better prognoses than patients with self-detected melanomas. Patients with melanomas that were self-detected by women had better prognoses than those that were self-detected by men, especially for patients >70 years of age. This group might therefore be a logical target for melanoma detection education.

15 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.

16 Article Exclusion criteria vs reality: dual BRAF/MEK inhibition and radiotherapy in a patient with melanoma metastatic to the brain and ECOG 3. 2016

Márquez-Rodas, Iván / Avilés-Izquierdo, Jose-Antonio / Parra, Verónica / Álvarez-González, Ana / Borrego, Pedro / Fernández-García, Pilar / Guzmán-de-Villoria, Juan-Adan / Jerez, Yolanda / Martin, Miguel. ·The Service of Medical Oncology, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid - Spain. · The Service of Dermatology, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid - Spain. · The Service of Anatomo-Pathology, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid - Spain. · The Service of Oncology-Radiotherapy, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid - Spain. · The Service of Radio-diagnostics, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid - Spain. ·Tumori · Pubmed #26350195.

ABSTRACT: BACKGROUND: Prognosis of metastatic melanoma is changing due to advances in immunotherapy and targeted therapy. However, management of patients with brain metastases in day-to-day practice continues to be a challenge. CASE REPORT: We describe a 40-year-old woman diagnosed with symptomatic brain metastases from cutaneous melanoma and Eastern Cooperative Oncology Group 3. She was treated, off label, with BRAF inhibitor (dabrafenib) + MEK inhibitor (trametinib) and radiotherapy. There was significant, long-lasting, response (17 months), no clinically relevant toxicity, and clear improvement in quality of life. CONCLUSIONS: This case is an example of real-life application of advances in targeted therapy.

17 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.

18 Article Metastatic melanoma with spontaneous regression, psoriasis and HLA-Cw6: case report and a hypothesis to explore. 2014

Pérez Ramírez, Sara / Parra, Verónica / Avilés Izquierdo, José Antonio / Vicario, José Luis / Martín, Miguel / Márquez-Rodas, Iván. · ·Tumori · Pubmed #25296606.

ABSTRACT: Spontaneous regressions of metastatic melanoma are rare, but several cases have been described in the literature. Although the mechanism of the phenomenon is not well understood, it is postulated that an activation of the immune system is behind it. Here we report the case of a patient with metastatic melanoma that, without any treatment, regressed spontaneously. The patient presented psoriasis (a disease of the skin related with autoimmunity) linked with HLA-Cw6. We review the literature and hypothesize with the possible relationship between psoriasis, HLA-Cw6 and the spontaneous regression.

19 Article Epidemiological changes in cutaneous melanoma: retrospective study of 969 cases (1996-2010). 2013

Avilés-Izquierdo, J A / Lázaro-Ochaita, P / Suárez-Fernández, R / Márquez-Rodas, I / Parra-Blanco, V / Escat-Cortés, J L. ·Servicio de Dermatología, Hospital General Universitario Gregorio Marañón, Madrid, Spain. jaavilesizquierdo@gmail.com ·Rev Clin Esp (Barc) · Pubmed #22874464.

ABSTRACT: BACKGROUND: The incidence of malignant melanoma has increased over recent decades all over the world; however, we are not aware if this also occurs in Madrid. Our objective was to analyze epidemiological changes in cutaneous malignant melanomas diagnosed over a 15-year period. PATIENTS AND METHODS: Retrospective analysis of data of patients with primary cutaneous melanomas attended at Hospital Gregorio Marañón, Madrid, Spain, between 1996 and 2010, divided into three periods: 1996-2000; 2001-2005; 2006-2010, was obtained. RESULTS: In total, 969 melanomas were histologically diagnosed. The mean age at the moment of diagnosis was 58.5 years old. The mean tumor thickness was 1.61 mm. The most common histological type was surface-spreading melanoma and the most common site was the trunk. There were statistically significant differences (P < .05) between the three periods of the study: older age at diagnoses (P < .001); larger number of head and neck melanomas (P < .001); more melanomas on trunk in women (P < .001); increase of lentigo maligna melanoma (P < .001); thinner mean tumor thickness (Breslow index) (P < .001); larger number of melanomas in situ (P < .001). However, thick melanomas (tumor thickness over 2 mm) ratio was still over 20% in all periods, especially in males and in those over 65 years old. CONCLUSIONS: Diagnosis of cutaneous melanoma in Spain is made increasingly with a thinner mean tumor thickness, although thick melanomas are still diagnosed in men and in individuals over 65 years.

20 Minor Why do patients with thick melanoma have different outcomes? A retrospective epidemiological and survival analysis. 2017

Rodríguez-Lomba, E / Marquez-Rodas, I / Mercader-Cidoncha, E / Suárez-Fernández, R / Avilés-Izquierdo, J A. ·Department of Dermatology, Hospital General Universitario Gregorio Marañón, C/Doctor Esquerdo, 46, 28007, Madrid, Spain. enriquerlomba@outlook.com. · Department of Medical Oncology, Hospital General Universitario Gregorio Marañón, Madrid, Spain. · Department of Surgery, Hospital General Universitario Gregorio Marañón, Madrid, Spain. · Department of Dermatology, Hospital General Universitario Gregorio Marañón, C/Doctor Esquerdo, 46, 28007, Madrid, Spain. ·Clin Transl Oncol · Pubmed #28251497.

ABSTRACT: -- No abstract --

21 Minor [Melanoma of male urethra: A clinical case]. 2010

Cabezón Gutiérrez, L / Márquez-Rodas, I / Soria Lovelle, A / Martín Marino, A / Alvarez Alvarez, R / Muñoz Martín, A J. · ·Actas Urol Esp · Pubmed #20540890.

ABSTRACT: -- No abstract --