FREE ACCESS TO THE LATEST RESEARCH
Welcome to the European Journal of Cancer’s Advances in Melanoma Resource Centre.
The Resource Centre, edited by Prof. Reinhard Dummer, Dr. Paolo Ascierto and Dr. James Larkin, will provide you with the latest research on melanoma, including a selection of original research and review articles from some of the world’s leading journals, case studies, and other educational material.
New articles will be added to the Resource Centre regularly and are openly available to our readers.
Paper of the month
Combination of vemurafenib and cobimetinib in patients with advanced BRAF V600-mutated melanoma: a phase 1b study
Antoni Ribas, Rene Gonzalez, Anna Pavlick, Omid Hamid, Thomas F Gajewski, Adil Daud, Lawrence Flaherty, Theodore Logan, Bartosz Chmielowski, Karl Lewis, Damien Kee, Peter Boasberg, Ming Yin, Iris Chan, Luna Musib, Nicholas Choong, Igor Puzanov, Grant A McOriginal Research Article The Lancet Oncology, Volume 15, Issue 9, August 2014, Pages 954-965
This is a dose-escalation phase I trial which enrolled 129 patients with advanced melanoma BRAFV600 mutant; all these patients were divided in two different cohorts: the previously treated with BRAF inhibitors and the naive to BRAF inhibitors treatment. They received vemurafenib and cobimetinib at progressively increasing doses in the different cohorts and the maximum tolerated dose established for the combination corresponds to that of the two drugs in monotherapy. The toxicity profile was acceptable with the reduction of some peculiar side effects of BRAF inhibitors, such as squamous cell carcinomas, compared with data from studies of vemurafenib monotherapy. This was probably due to the attenuation of the paradoxal BRAF-induced activation of the MAPK pathway in normal tissues, induced by the simultaneous inhibition of MEK. The combination therapy in vemurafenib-naive patients has given encouraging results. The most significant data is certainly the PFS of 13 months much higher than that of 6-7 months obtained with vemurafenib monotherapy. Of course this finding requires confirmation in the ongoing phase III trial.
Sara Tomei, Davide Bedognetti, Valeria De Giorgi, Michele Sommariva, Sara Civini, Jennifer Reinboth, Muna Al Hashmi, Maria Libera Ascierto, Qiuzhen Liu, Ben D. Ayotte, Andrea Worschech, Lorenzo Uccellini, Paolo A. Ascierto, David Stroncek, Giuseppe PalmieOriginal Research Article Molecular Oncology, In Press, Uncorrected Proof, Available online 6 August 2014
The role of oncogenes BRAF and NRAS has been extensively described with regard to their ability to promote tumor growth. It is not yet clear their role to influence the modulation of the immune response against the tumor. In this study it was investigated the correlation between the presence NRAS or BRAF mutation, the gene expression profile and the presence of one of the two different immune phenotypes, the Th17 and the Th1, which were previously connected to different classes of prognosis. According to this study, the BRAF mutation was associated with a worse prognosis immunophenotype, while there was no clear correlation between the mutation of NRAS and the context of tumor immunology. Despite the great interest of these results, it remains unclear what are the mechanisms that underlie this association and what are the possible clinical implications.
No longer an untreatable disease: How targeted and immunotherapies have changed the management of melanoma patients
Maria Romina Girotti, Grazia Saturno, Paul Lorigan, Richard MaraisReview Article Molecular Oncology, In Press, Uncorrected Proof, Available online 15 August 2014
This is a review which comprehensively covers the enormous progress made in recent years in the treatment of metastatic melanoma. Starting from the explanation of the biological mechanisms which underlie them, the authors clearly illustrate the basis in the development of the various target therapies, in particular BRAF and MEK inhibitors, and the different immunotherapeutic drugs, first of all the anti-CTLA-4 ipilimumab, followed by anti-PD-1 and anti-PD-L1, not forgetting to emphasize the importance of combination therapy, which are currently the main hope for further future progress.
BRAF mutation status is an independent prognostic factor for resected stage IIIB and IIIC melanoma: Implications for melanoma staging and adjuvant therapy
Andrew P. Barbour, Yue Hang Tang, Nicola Armour, Ken Dutton-Regester, Lutz Krause, Kelly A. Loffler, Duncan Lambie, Bryan Burmeister, Janine Thomas, B. Mark Smithers, Nicholas K. Hayward
European Journal of Cancer
This interesting work shows the data obtained from the analysis of a prospective database with Stage IIIA-C cutaneous melanoma patients who underwent to TLND surgery from 1997 onwards at the Princess Alexandra Hospital and with a follow-up of 10 years. The authors explored the correlation between the presence of oncogenic mutations and patient outcomes in terms of median recurrence-free and disease-specific survival. The BRAF mutation and the number of involved lymph nodes appeared to be the only two prognostic factors identified. In particular, the rapid recurrence who experience patients with BRAF mutation and the fact that this occurrence is generally systemic and not locoregional, supports the hypothesis that in this subgroup of patients might be useful an adjuvant therapy with BRAF inhibitors in order to improve their prognosis.
About the editors
Professor Reinhard G. Dummer
Professor Dummer is Vice-Chairman of the Department of Dermatology and Head of the Skin Cancer Unit at the University Hospital of Zürich.
Dr. James Larkin
Dr James Larkin, FRCP PhD is a Medical Oncologist specialising in the treatment
of patients with cancer of the kidney and cancers of the skin, including melanoma
Dr. Paolo A. Ascierto
Dr. Paolo A. Ascierto is Director at the Unit of Melanoma, Cancer Immunotherapy and Innovative Therapy, National Tumor Institute ‘Fondazione G. Pascale’, in Naples, Italy.