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Melanoma: HELP
Articles by A. Arance
Based on 12 articles published since 2010
(Why 12 articles?)
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Between 2010 and 2020, A. Arance wrote the following 12 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 Guideline Guidelines for biomarker testing in metastatic melanoma: a National Consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology. 2014

Martín-Algarra, S / Fernández-Figueras, M T / López-Martín, J A / Santos-Briz, A / Arance, A / Lozano, M D / Berrocal, A / Ríos-Martín, J J / Espinosa, E / Rodríguez-Peralto, J L / Anonymous3550772 / Anonymous3560772. ·Medical Oncology Department, Clínica Universidad de Navarra, Avenida de Pio XII, 36, 31008, Pamplona, Spain, smalgarra@unav.es. ·Clin Transl Oncol · Pubmed #24129426.

ABSTRACT: This consensus statement, conceived as a joint initiative of the Spanish Society of Pathology (SEAP) and the Spanish Society of Medical Oncology (SEOM), makes diagnostic and treatment recommendations for the management of patients with advanced or metastatic melanoma based on the current scientific evidence on biomarker use. This document thus provides an opportunity to improve healthcare efficiency and resource use, which will benefit these patients. Based on the data available so far, this expert group recommends routinely testing patients with metastatic melanoma for BRAF mutation status, as the result affects the subsequent therapeutic management of these patients. The analysis of genetic alterations in KIT may be reasonable in patients with primary tumours in acral or mucosal sites or on chronically sun-exposed skin, in an advanced condition, but not in patients with other types of melanomas. This panel believes that testing for other genetic alterations, such as NRAS mutation status in patients not carrying BRAF mutations, GNAQ/GNA11 mutational analysis or genetic alterations in PTEN, is not currently indicated as routine clinical practice, because the results do not influence treatment planning in these patients at the present time. Other important issues addressed in this document are the organisational requirements and quality controls needed for proper testing of these biomarkers, and the legal implications to be borne in mind.

3 Clinical Trial Dabrafenib plus trametinib versus dabrafenib monotherapy in patients with metastatic BRAF V600E/K-mutant melanoma: long-term survival and safety analysis of a phase 3 study. 2017

Long, G V / Flaherty, K T / Stroyakovskiy, D / Gogas, H / Levchenko, E / de Braud, F / Larkin, J / Garbe, C / Jouary, T / Hauschild, A / Chiarion-Sileni, V / Lebbe, C / Mandalà, M / Millward, M / Arance, A / Bondarenko, I / Haanen, J B A G / Hansson, J / Utikal, J / Ferraresi, V / Mohr, P / Probachai, V / Schadendorf, D / Nathan, P / Robert, C / Ribas, A / Davies, M A / Lane, S R / Legos, J J / Mookerjee, B / Grob, J-J. ·Melanoma Institute Australia, The University of Sydney, and Royal North Shore and Mater Hospitals, North Sydney, Australia. · Developmental Therapeutics and Melanoma Programs, Massachusetts General Hospital Cancer Center, Boston, USA. · Moscow City Oncology Hospital #62, Moscow, Russia. · First Department of Medicine, "Laiko" General Hospital, National and Kapodistrian University of Athens, Athens, Greece. · Petrov Research Institute of Oncology, Saint Petersburg, Russia. · Dipartimento di Medicina Oncologica, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. · Royal Marsden NHS Foundation Trust, London, UK. · Department of Dermatology, University of Tübingen, Tübingen, Germany. · Service D'oncologie Médicale, Hopital Francois Mitterrand, Pau, France. · Department of Dermatology, University Hospital Schleswig-Holstein, Kiel, Germany. · Melanoma and Oesophageal Oncology Unit, Veneto Oncology Institute-IRCCS, Padova, Italy. · APHP Dermatology and CIC Departments, INSERM U976, University Paris Diderot, Paris, France. · Department of Oncology and Hematology, Papa Giovanni XXIII Hospital, Bergamo, Italy. · Medical Oncology Department, Sir Charles Gairdner Hospital, Perth, Australia. · Department of Medical Oncology, Hospital Clinic of Barcelona, Barcelona, Spain. · Dnipropetrovsk State Medical Academy, Clinical Hospital #4, Dnipropetrovsk, Ukraine. · Netherlands Cancer Institute, Amsterdam, The Netherlands. · Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. · Skin Cancer Unit, German Cancer Research Center (DKFZ) and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karls University of Heidelberg, Mannheim and Heidelberg, Germany. · Department of Medical Oncology A, Regina Elena National Cancer Institute, Rome, Italy. · Dermatologisches Zentrum Buxtehude, Elbe Kliniken Buxtehude, Buxtehude, Germany. · Dnipropetrovsk Clinical Oncology Center of Dnipropetrovsk State Council, Dnipropetrovsk, Ukraine. · Department of Dermatology, University Hospital Essen, Essen, Germany. · German Cancer Consortium, Heidelberg, Germany. · Mount Vernon Cancer Centre, Northwood, UK. · Gustave Roussy, Département de Médecine Oncologique, Service de Dermatologie et Université Paris-Sud, Faculté de Médecine, Villejuif, France. · Department of Medicine, Hematology/Oncology, UCLA Jonsson Comprehensive Cancer Center, Los Angeles, USA. · Melanoma Medical Oncology and Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, USA. · Novartis Pharmaceuticals Corporation, East Hanover, USA. · Service de Dermatologie, Centre Hospitalo-Universitaire Timone, Aix-Marseille Université, Marseille, France. ·Ann Oncol · Pubmed #28475671.

ABSTRACT: Background: Previous analysis of COMBI-d (NCT01584648) demonstrated improved progression-free survival (PFS) and overall survival (OS) with combination dabrafenib and trametinib versus dabrafenib monotherapy in BRAF V600E/K-mutant metastatic melanoma. This study was continued to assess 3-year landmark efficacy and safety after ≥36-month follow-up for all living patients. Patients and methods: This double-blind, phase 3 study enrolled previously untreated patients with BRAF V600E/K-mutant unresectable stage IIIC or stage IV melanoma. Patients were randomized to receive dabrafenib (150 mg twice daily) plus trametinib (2 mg once daily) or dabrafenib plus placebo. The primary endpoint was PFS; secondary endpoints were OS, overall response, duration of response, safety, and pharmacokinetics. Results: Between 4 May and 30 November 2012, a total of 423 of 947 screened patients were randomly assigned to receive dabrafenib plus trametinib (n = 211) or dabrafenib monotherapy (n = 212). At data cut-off (15 February 2016), outcomes remained superior with the combination: 3-year PFS was 22% with dabrafenib plus trametinib versus 12% with monotherapy, and 3-year OS was 44% versus 32%, respectively. Twenty-five patients receiving monotherapy crossed over to combination therapy, with continued follow-up under the monotherapy arm (per intent-to-treat principle). Of combination-arm patients alive at 3 years, 58% remained on dabrafenib plus trametinib. Three-year OS with the combination reached 62% in the most favourable subgroup (normal lactate dehydrogenase and <3 organ sites with metastasis) versus only 25% in the unfavourable subgroup (elevated lactate dehydrogenase). The dabrafenib plus trametinib safety profile was consistent with previous clinical trial observations, and no new safety signals were detected with long-term use. Conclusions: These data demonstrate that durable (≥3 years) survival is achievable with dabrafenib plus trametinib in patients with BRAF V600-mutant metastatic melanoma and support long-term first-line use of the combination in this setting.

4 Clinical Trial Efficacy and safety of nilotinib in patients with KIT-mutated metastatic or inoperable melanoma: final results from the global, single-arm, phase II TEAM trial. 2017

Guo, J / Carvajal, R D / Dummer, R / Hauschild, A / Daud, A / Bastian, B C / Markovic, S N / Queirolo, P / Arance, A / Berking, C / Camargo, V / Herchenhorn, D / Petrella, T M / Schadendorf, D / Sharfman, W / Testori, A / Novick, S / Hertle, S / Nourry, C / Chen, Q / Hodi, F S. ·Department of Renal Cancer & Melanona, Peking University Cancer Hospital & Institute, Beijing, China. · Division of Hematology/Oncology, Columbia University Medical Center, New York, USA. · Skin Cancer Center, University Hospital of Zurich, Zurich, Switzerland. · Department of Dermatology, University Hospital Schleswig-Holstein (UKSH), Campus Kiel, Kiel, Germany. · Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco. · Department of Hematology/Oncology, Mayo Clinic Cancer Center, Rochester, USA. · Department of Medical Oncology, National Research Institute for Cancer, Genova, Italy. · Department of Medical Oncology, Hospital Clinic, Barcelona, Spain. · Department of Dermatology & Allergology, University Hospital Munich (LMU), Munich, Germany. · Department of Medical Oncology, Cancer Institute of São Paulo, São Paulo. · Department of Clinical Oncology, National Institute of Cancer, Rio de Janeiro, Brazil. · Department of Medical Oncology, Sunnybrook Health Sciences Center, Toronto, Canada. · Department of Dermatology, Essen University Hospital, Essen, Germany. · Department of Oncology & Dermatology, Sidney Kimmel Comprehensive Cancer Center/Johns Hopkins Medicine, Lutherville, USA. · Melanoma and Muscle Cutaneous Sarcoma Division, European Institute of Oncology, Milano, Italy. · Oncology Business Unit, Novartis Pharmaceuticals Corporation, East Hanover, USA. · Oncology Business Unit, Novartis Pharma AG, Basel, Switzerland. · Melanoma Center, Dana-Farber Cancer Institute, Boston, USA. ·Ann Oncol · Pubmed #28327988.

ABSTRACT: Background: The single-arm, phase II Tasigna Efficacy in Advanced Melanoma (TEAM) trial evaluated the KIT-selective tyrosine kinase inhibitor nilotinib in patients with KIT-mutated advanced melanoma without prior KIT inhibitor treatment. Patients and methods: Forty-two patients with KIT-mutated advanced melanoma were enrolled and treated with nilotinib 400 mg twice daily. TEAM originally included a comparator arm of dacarbazine (DTIC)-treated patients; the design was amended to a single-arm trial due to an observed low number of KIT-mutated melanomas. Thirteen patients were randomized to DTIC before the protocol amendment removing this study arm. The primary endpoint was objective response rate (ORR), determined according to Response Evaluation Criteria In Solid Tumors. Results: ORR was 26.2% (n = 11/42; 95% CI, 13.9%-42.0%), sufficient to reject the null hypothesis (ORR ≤10%). All observed responses were partial responses (PRs; median response duration, 7.1 months). Twenty patients (47.6%) had stable disease and 10 (23.8%) had progressive disease; 1 (2.4%) response was unknown. Ten of the 11 responding patients had exon 11 mutations, four with an L576P mutation. The median progression-free survival and overall survival were 4.2 and 18.0 months, respectively. Three of the 13 patients on DTIC achieved a PR, and another patient had a PR following switch to nilotinib. Conclusion: Nilotinib activity in patients with advanced KIT-mutated melanoma was similar to historical data from imatinib-treated patients. DTIC treatment showed potential activity, although the low patient number limits interpretation. Similar to previously reported results with imatinib, nilotinib showed greater activity among patients with an exon 11 mutation, including L576P, suggesting that nilotinib may be an effective treatment option for patients with specific KIT mutations. Clinical Trial Registration: ClinicalTrials.gov, NCT01028222.

5 Clinical Trial Vemurafenib in metastatic melanoma patients with brain metastases: an open-label, single-arm, phase 2, multicentre study. 2017

McArthur, G A / Maio, M / Arance, A / Nathan, P / Blank, C / Avril, M-F / Garbe, C / Hauschild, A / Schadendorf, D / Hamid, O / Fluck, M / Thebeau, M / Schachter, J / Kefford, R / Chamberlain, M / Makrutzki, M / Robson, S / Gonzalez, R / Margolin, K. ·Department of Medical Oncology, Peter MacCallum Cancer Centre, East Melbourne and University of Melbourne, Parkville, Australia. · AOU Senese Policlinico Santa Maria Alle Scotte, Siena, Italy. · Department of Medical Oncology, Hospital Clínic Barcelona, Spain. · Mount Vernon Hospital, Centre for Cancer Treatment, Northwood, UK. · The Netherlands Cancer Institute, Amsterdam, The Netherlands. · University Paris Descartes, Hospital Cochin, APHP, Paris, France. · Department of Dermatology, University Hospital Tuebingen, Tuebingen. · Department of Dermatology, University Hospital Schleswig-Holstein (UKSH), Campus Kiel, Kiel. · Department of Dermatology, Comprehensive Cancer Center, University Hospital Essen, Essen, Germany. · Angeles Clinic and Research Institute, Los Angeles, USA. · Fachklinik Hornheide, Munster, Germany. · Moffitt Cancer Center, Tampa, USA. · Chaim Sheba Medical Centre, Oncology Institute, Ramat-Gan, Israel. · Crown Princess Cancer Centre Westmead Hospital and Department of Clinical Medicine, Macquarie University, Sydney NSW, Australia. · Seattle Cancer Care Alliance, Seattle, USA. · F. Hoffmann-La Roche Ltd, Basel, Switzerland. · University of Colorado Cancer Center, Aurora. · City of Hope, Duarte, USA. ·Ann Oncol · Pubmed #27993793.

ABSTRACT: Background: Vemurafenib has shown activity in patients with BRAFV600 mutated melanoma with brain metastases (BM). This phase 2 study evaluated vemurafenib in patients with/without prior treatment for BM. Methods: Patients with BRAFV600 mutated melanoma with BM were enrolled into cohort 1 (previously untreated BM) and cohort 2 (previously treated BM) and received vemurafenib (960 mg BID) until disease progression (PD) or intolerance. Primary endpoint was best overall response rate (BORR) in the brain in cohort 1 that was evaluated using modified RECIST 1.1 criteria using lesions ≥0.5 cm to assess response. Results: 146 patients were treated (cohort 1 n = 90; cohort 2 n = 56), 62% of whom were male. Median (range) time since diagnosis of BM: 1.0 (0-9) month in cohort 1 and 4.2 (1-68) months in cohort 2. Median duration of treatment was 4.1 months (range 0.3-34.5) in cohort 1 and 4.1 months (range 0.2-27.6) in cohort 2. Intracranial BORR in cohort 1 by an independent review committee (IRC) was 18% (2 CRs, 14 PRs). Extracranial BORR by IRC was 33% in cohort 1 and 23% in cohort 2. Median PFS (brain only, investigator-assessed) was 3.7 months (range 0.03-33.4; IQR 1.9-5.6) in cohort 1 and 4.0 months (range 0.3-27.4; IQR 2.2-7.4) in cohort 2. Median OS was 8.9 months (range 0.6-34.5; IQR 4.9-17.0) in cohort 1 and 9.6 months (range 0.7-34.3; IQR 4.5-18.4) in cohort 2. Adverse events (AEs) were similar in type, grade and frequency to other studies of single-agent vemurafenib. Grade 3/4 AEs occurred in 59 (66%) patients in cohort 1 and 36 (64%) in cohort 2. Overall, 84% of patients died during the study (86% in cohort 1 and 80% in cohort 2), mainly due to disease progression. Conclusions: The study demonstrates clinically meaningful response rates of melanoma BM to vemurafenib, which was well tolerated and without significant CNS toxicity.

6 Article A retrospective chart review study describing metastatic melanoma patients profile and treatment patterns in Spain. 2019

Márquez-Rodas, I / Arance, A / Berrocal, A / Larios, C L / Curto-García, J / Campos-Tapias, I X / Blanca, A B / Martin-Algarra, S. ·Medical Oncology, Hospital General Universitario Gregorio Marañón, Calle Dr. Esquerdo 46, 28007, Madrid, Spain. ivanpantic@hotmail.com. · CIBERONC, Madrid, Spain. ivanpantic@hotmail.com. · Medical Oncology, Hospital Clínic Barcelona, Barcelona, Spain. · Medical Oncology, Hospital General Universitario de Valencia, Valencia, Spain. · Clinical Research Department, MFAR S.L, Barcelona, Spain. · AMGEN S.A, Barcelona, Spain. · Medical Oncology, Clínica Universidad de Navarra, Pamplona, Spain. ·Clin Transl Oncol · Pubmed #31435877.

ABSTRACT: PURPOSE: To describe patient characteristics by disease stage, resectability status and current treatment management after first diagnosis of IIIB to IV1c advanced (AM)/metastatic melanoma (MM). METHODS/PATIENTS: Multicentre, retrospective study based on data from medical charts of patients > 18 years at MM first diagnosis, visited by oncologists at 4 reference centres in Spain: Hospital Universitario Gregorio Marañón (Madrid), Hospital General de Valencia (Valencia), Clínica Universidad de Navarra (Pamplona), and Hospital Clínic (Barcelona). RESULTS: Metastatic non-visceral melanoma (IIIB, IIIC, IV M1a) was reported in 139 (48.6%) patients and 40.9% (n = 117) were diagnosed with IV-M1c disease. 160 (55.9%) metastases were resectable. Available therapies under clinical practice were used in 210 patients; 74 were treated under clinical trials (CT). Intention-to-cure surgery (47.6%) was the most common treatment at time of MM diagnosis. Systemic (45.1% overall) therapy included chemo-, targeted- and immunotherapy (19.6%, 14.3%, 8.4%, respectively). At time of data collection, 26 patients were still alive and 120 had progressed to IV-M1c. Median overall survival (OS) was significantly larger in IIIB patients, 28.9 m (25.2-32.7); the shortest for IV-M1c patients, 11.0 m (8.7-13.3). CONCLUSIONS: Novel treatments are undoubtedly a major step forward in AM/MM, however these are often only available in the CT setting because early stages of development or country-specific regulations. Further prospective studies and multifactorial analysis should be performed to clearly identify possible clinical associations for outcome in Spanish patients with AM/MM.

7 Article Discontinuation of anti-PD-1 antibody therapy in the absence of disease progression or treatment limiting toxicity: clinical outcomes in advanced melanoma. 2019

Jansen, Y J L / Rozeman, E A / Mason, R / Goldinger, S M / Geukes Foppen, M H / Hoejberg, L / Schmidt, H / van Thienen, J V / Haanen, J B A G / Tiainen, L / Svane, I M / Mäkelä, S / Seremet, T / Arance, A / Dummer, R / Bastholt, L / Nyakas, M / Straume, O / Menzies, A M / Long, G V / Atkinson, V / Blank, C U / Neyns, B. ·Department of Medical Oncology, Universitair Ziekenhuis Brussel, Brussel, Belgium. · Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. · Department of Medical Oncology, Princess Alexandra Hospital, Brisbane. · Greenslope Oncology, Greenslope Private Hospital, Brisbrane. · Melanoma Institute Australia and The University of Syndey, Sydney, Australia. · Department of Dermatology, University Hospital Zurich, Zurich, Switzerland. · Department of Oncology, Odense University Hospital, Odense. · Department of Oncology, Aarhus Universitet, Aarhus, Denmark. · Department of Oncology, Tampere University Hospital, Tampere, Finland. · Department of Oncology, Copenhagen University Hospital, Herlev, Denmark. · Department of Oncology, University of Helsinki, Helsinki, Finland. · Department of Medical Oncology, Hospital Clínic Barcelona, Barcelona, Spain. · Department of Clinical Cancer Research, Oslo University Hospital, Oslo. · Department of Oncology, Universitetet Bergen, Bergen, Norway. · Department of Medical Oncology, Northern Sydney Cancer Centre, Royal North Shore Hospital, Sydney. · Department of Medical Oncology, Mater Hospital, Sydney, Australia. ·Ann Oncol · Pubmed #30923820.

ABSTRACT: BACKGROUND: Programmed cell death protein 1 (PD-1) blocking monoclonal antibodies improve the overall survival of patients with advanced melanoma but the optimal duration of treatment has not been established. PATIENTS AND METHODS: This academic real-world cohort study investigated the outcome of 185 advanced melanoma patients who electively discontinued anti-PD-1 therapy with pembrolizumab (N = 167) or nivolumab (N = 18) in the absence of disease progression (PD) or treatment limiting toxicity (TLT) at 14 medical centres across Europe and Australia. RESULTS: Median time on treatment was 12 months (range 0.7-43). The best objective tumour response at the time of treatment discontinuation was complete response (CR) in 117 (63%) patients, partial response (PR) in 44 (24%) patients and stable disease (SD) in 16 (9%) patients; 8 (4%) patients had no evaluable disease (NE). After a median follow-up of 18 months (range 0.7-48) after treatment discontinuation, 78% of patients remained free of progression. Median time to progression was 12 months (range 2-23). PD was less frequent in patients with CR (14%) compared with patients with PR (32%) and SD (50%). Six out of 19 (32%) patients who were retreated with an anti-PD-1 at the time of PD obtained a new antitumour response. CONCLUSIONS: In this real-world cohort of advanced melanoma patients discontinuing anti-PD-1 therapy in the absence of TLT or PD, the duration of anti-PD-1 therapy was shorter when compared with clinical trials. In patients obtaining a CR, and being treated for >6 months, the risk of relapse after treatment discontinuation was low. Patients achieving a PR or SD as best tumour response were at higher risk for progression after discontinuing therapy, and defining optimal treatment duration in such patients deserves further study. Retreatment with an anti-PD-1 at the time of progression may lead to renewed antitumour activity in some patients. CLINICAL TRIAL REGISTRATION: NCT02673970 (https://clinicaltrials.gov/ct2/show/NCT02673970?cond=melanoma&cntry=BE&city=Jette&rank=3).

8 Article Real-world treatment patterns and outcomes among metastatic cutaneous melanoma patients treated with ipilimumab. 2018

Mohr, P / Ascierto, P / Arance, A / McArthur, G / Hernaez, A / Kaskel, P / Shinde, R / Stevinson, K. ·Elbe-Klinikum Buxtehude, Buxtehude, Germany. · Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy. · Hospital Clinic Barcelona, Barcelona, Spain. · Peter MacCallum Cancer Centre, East Melbourne, Vic., Australia. · University of Melbourne, Parkville, Vic., Australia. · Mapi, Stockholm, Sweden. · MSD SHARP & DOHME GMBH, Haar, Germany. · Merck & Co. Inc., Kenilworth, NJ, USA. ·J Eur Acad Dermatol Venereol · Pubmed #29044660.

ABSTRACT: BACKGROUND: There is a scarcity of real-world data on treatment patterns and outcomes among advanced melanoma patients treated with immunotherapies including ipilimumab, an anti-CTLA-4 antibody approved since 2011. OBJECTIVE: To evaluate ipilimumab and postipilimumab treatment patterns and outcomes among patients with advanced melanoma in Australia, Germany, Italy and Spain, following regulatory approval. METHODS: Retrospective multicentre, multinational, observational chart review study. Data were extracted from the start of ipilimumab therapy until the end of at least 40 weeks of follow-up, or death. RESULTS: Data from 371 patients (Australia, 103; Germany, 152; Italy, 76; Spain, 40) were analysed. Mean age was 65 years; 62% were male. Eastern Cooperative Oncology Group performance status (ECOG PS) was 0 or 1 for 94%. In 67%, ipilimumab was initially received as second-line or later therapy. Patients received on average 3.4 ipilimumab doses. The ipilimumab-refractory cohort comprised of 226 patients. Of these, 17% in Australia, 47% in Germany, 29% in Italy and 14% in Spain received another antimelanoma treatment after ipilimumab including chemotherapy in 26% and BRAF/other kinase inhibitors in 11%. Ipilimumab-refractory patients who received postipilimumab treatment showed a 40% reduced hazard of dying than those not receiving treatment after ipilimumab (HR 0.60; 95% CI 0.43-0.83), after adjustment for potential confounders. CONCLUSION: During the time observed, ipilimumab was mainly used as second-line or later therapy. A significant proportion of patients received postipilimumab therapy, most of which was chemotherapy. Nevertheless, overall survival following progression on ipilimumab treatment remained poor, highlighting the need for research to develop more effective end-of-life treatment options.

9 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 / Anonymous3720892. ·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.

10 Article Sequential treatment with immunotherapy and BRAF inhibitors in BRAF-mutant advanced melanoma. 2017

Aya, F / Fernandez-Martinez, A / Gaba, L / Victoria, I / Tosca, M / Pineda, E / Gascon, P / Prat, A / Arance, A. ·Department of Medical Oncology, Hospital Clínic, Barcelona, Spain. faya@clinic.ub.es. · Translational Genomics and Targeted Therapeutics in Solid Tumors, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. faya@clinic.ub.es. · Department of Medical Oncology, Hospital Clínic, Barcelona, Spain. · Translational Genomics and Targeted Therapeutics in Solid Tumors, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. ·Clin Transl Oncol · Pubmed #27147251.

ABSTRACT: PURPOSE: Immunotherapy (IT) agents and BRAF inhibitors (BRAFi) are effective treatments for patients with advanced BRAF-mutant melanoma although the optimal sequence remains to be elucidated. The aim of this study was to compare the outcomes of two different cohorts of patients treated with BRAFi first, then IT or the reverse sequence. PATIENTS AND METHODS: This is a retrospective study on two groups of patients: a cohort was treated first with BRAFi followed by immunotherapy (BRAFi-IT) and the other cohort with the reverse sequence (IT-BRAFi). Baseline characteristics and clinical outcomes were compared between the two cohorts. RESULTS: A total of 25 patients were included in the study. Sixteen patients were given BRAFi-IT sequence and nine received IT-BRAFi sequence. No differences were observed in the characteristics of patients prior to each treatment between cohorts. Objective response rate (ORR) achieved by BRAFi were not different among groups. ORR achieved by IT was higher when administered after BRAFi (43.8 vs 0 %). Survival rates at 1-2 years were similar in both cohorts and median overall survival was not different for BRAFi-IT and IT-BRAFi (log rank test p = 0.97). CONCLUSIONS: No differences were observed in OS between the two cohorts. These results support the indistinct use of IT or BRAFi as initial treatment in patients with metastatic BRAF-mutant melanoma, although higher rate of response to IT was observed when administered after BRAFi. Prospective randomized clinical trials are needed on this issue.

11 Article SEOM guidelines for the management of Malignant Melanoma 2015. 2015

Berrocal, A / Arance, A / Espinosa, E / Castaño, A G / Cao, M G / Larriba, J L G / Martín, J A L / Márquez, 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 Universitario la Paz, Madrid, Spain. · Hospital Universitario Marqués de Valdecilla, Santander, Spain. · Hospital Universitario Quirón Dexeus, Barcelona, Spain. · Hospital Universitario Clínico San Carlos, Madrid, Spain. · Hospital Universitario 12 de Octubre, 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 #26669314.

ABSTRACT: All melanoma patients must be confirmed histologically and resected according to Breslow. Sentinel node biopsy must be done when tumor is over 1 mm or if less with high-risk factors. Adjuvant therapy with interferon must 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 therapy and BRAF mutated patients BRAF/MEK inhibitors or anti-PD1 therapy. Up to 10 years follow up is recommended for melanoma patients with dermatologic examinations and physical exams.

12 Minor Vasculitic neuropathy induced by pembrolizumab. 2017

Aya, F / Ruiz-Esquide, V / Viladot, M / Font, C / Prieto-González, S / Prat, A / Arance, A. ·Medical Oncology Department, Hospital Clínic of Barcelona, Barcelona, Spain · Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute, Barcelona, Spain. · Arthritis Unit, Rheumatology Department, Hospital Clínic, IDIBAPS, Villarroel, 170, 08036 Barcelona, Spain. · Systemic Autoimmune Diseases, Vasculitis Research Unit, Hospital Clinic Barcelona. · Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. ·Ann Oncol · Pubmed #27864214.

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