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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 – Januari 2015

  • Nivolumab in Previously Untreated Melanoma without BRAF Mutation

    Caroline Robert, M.D., Ph.D., Georgina V. Long, M.D., Ph.D., Benjamin Brady, M.D., Et al

    N Engl J Med 2014, E-pub November 16, 2014,

    Editor's comments: Prof Paolo A. Ascierto
    Nivolumab is a fully human IgG4 anti PD-1 antibody that selectively blocks the interaction of the PD-1 receptor with its two ligands, PD-L1 and PD-L2, disrupting the negative signal which regulates T-cell activation and proliferation. In a phase I study nivolumab was associated with promising antitumor activity in patients with solid tumors, including advanced melanoma. In this manuscript were reported data of a randomized phase 3 double-blind study where nivolumab was compared to dacarbazine to verify whether it’s able to improve overall survival of previously untreated patients with advanced melanoma BRAF wild type. The study was largely positive showing a significant improvement of ORR (40 % vs 13.9%), PFS (5.1 vs 22 months) and 1-year OS (72.95 vs 42.1%) for the group of patients treated with nivolumab respect to those treated with dacarbazine. In addition to an high response rate, it was also found a long duration of responses (median DOR in the patients treated with nivolumab was not found yet), and a rapid time to response (2.1 months) with a good toxicity profile. Nivolumab treated patients had improved ORR as compared with dacarbazine treated patients both in PD-L1 positive and PD-L1 negative groups. In the subgroup with PD-L1 positive, the ORR was 52.7% in the nivolumab group versus 10.8% in the dacarbazine group. In the subgroup with PD-L1 negative, the ORR was 33.1% in the nivolumab group versus 15.7% in the dacarbazine group. The 1-year OS rate for the nivolumab PD-L1 positive, nivolumab PD-L1 negative, dacarbazine PD-L1 positive, and dacarbazine PD-L1 negative was of 82.1%, 67.8, 52.7, and 37.4 respectively. These data evidenced that PD-L1 positive status is related with a better survival but also PD-L1 negative patients had an higher OS respect to the control arm.

    When this study was planning ipilimumab wasn't still approved as first-line of treatment. Currently is ongoing a three-arms phase III study which is evaluating the combination of ipilimumab and nivolumab with nivolumab and ipilimumab monotherapy in previously untreated advanced melanoma patients.


Latest articles

  • Nivolumab in Previously Untreated Melanoma without BRAF Mutation

    Caroline Robert, M.D., Ph.D., Georgina V. Long, M.D., Ph.D., Benjamin Brady, M.D., Et al

    N Engl J Med 2014, E-pub November 16, 2014,

    Editor's comments: Prof Paolo A. Ascierto
    Nivolumab is a fully human IgG4 anti PD-1 antibody that selectively blocks the interaction of the PD-1 receptor with its two ligands, PD-L1 and PD-L2, disrupting the negative signal which regulates T-cell activation and proliferation. In a phase I study nivolumab was associated with promising antitumor activity in patients with solid tumors, including advanced melanoma. In this manuscript were reported data of a randomized phase 3 double-blind study where nivolumab was compared to dacarbazine to verify whether it’s able to improve overall survival of previously untreated patients with advanced melanoma BRAF wild type. The study was largely positive showing a significant improvement of ORR (40 % vs 13.9%), PFS (5.1 vs 22 months) and 1-year OS (72.95 vs 42.1%) for the group of patients treated with nivolumab respect to those treated with dacarbazine. In addition to an high response rate, it was also found a long duration of responses (median DOR in the patients treated with nivolumab was not found yet), and a rapid time to response (2.1 months) with a good toxicity profile. Nivolumab treated patients had improved ORR as compared with dacarbazine treated patients both in PD-L1 positive and PD-L1 negative groups. In the subgroup with PD-L1 positive, the ORR was 52.7% in the nivolumab group versus 10.8% in the dacarbazine group. In the subgroup with PD-L1 negative, the ORR was 33.1% in the nivolumab group versus 15.7% in the dacarbazine group. The 1-year OS rate for the nivolumab PD-L1 positive, nivolumab PD-L1 negative, dacarbazine PD-L1 positive, and dacarbazine PD-L1 negative was of 82.1%, 67.8, 52.7, and 37.4 respectively. These data evidenced that PD-L1 positive status is related with a better survival but also PD-L1 negative patients had an higher OS respect to the control arm.

    When this study was planning ipilimumab wasn't still approved as first-line of treatment. Currently is ongoing a three-arms phase III study which is evaluating the combination of ipilimumab and nivolumab with nivolumab and ipilimumab monotherapy in previously untreated advanced melanoma patients.

  • Improved Overall Survival in Melanoma with Combined Dabrafenib and Trametinib

    Caroline Robert, M.D., Ph.D., Boguslawa Karaszewska, M.D., Jacob Schachter, M.D., Et al.

    N Engl J Med 2015; 372:30-39 January 1, 2015

    Editor's comments: Prof Paolo A. Ascierto
    The advent of BRAF inhibitors for the treatment of metastatic melanoma harboring the BRAF V600 mutation has allowed to achieve significant results in terms of PFS and OS compared to standard chemotherapy. Unfortunately, the principal limitation of these treatments is the occurrence of acquired resistance due to the reactivation of the MAPK pathway. In addition, it is known that the use of BRAF inhibitors may result in the development of secondary skin tumors, due to a paradoxical activation of the MAPK pathway in cells with without a BRAF mutation but with NRAS mutated. The combination of a BRAF inhibitor with a MEK inhibitor could reduce both of these limitations of BRAF inhibitors monotherapy. The study presented in this manuscript is an open-label, randomized, phase 3 study enrolling 704 patients with unresectable stage IIIC or IV melanoma with BRAF V600E or V600K mutations, designed to evaluate the effect on overall survival of the combination therapy with dabrafenib plus trametinib versus vemurafenib monotherapy. The median overall survival was 17.2 months in the vemurafenib group while was not reached in the combination-therapy group; the risk reduction for progression or death was of 31%. A significant improvements were found also in terms of ORR and PFS. Skin adverse events were less frequent in the combination-therapy group: cutaneous squamous-cell carcinoma and keratoacanthoma occurred in 1% of patients in the combination-therapy group and 18% in the vemurafenib group. This finding confirms that the addition of MEK inhibitors may delay the treatment resistance and reduce the occurrence of skin cancers.

  • Paradox-Breaking RAF Inhibitors that Also Target SRC Are Effective in Drug-Resistant BRAF Mutant Melanoma

    Maria Romina Girotti, Filipa Lopes, Natasha Preece, Dan Niculescu-Duvaz, Alfonso Zambon, Lawrence Davies, Steven Whittaker, Grazia Saturno, Amaya Viros, Malin Pedersen, Bart M.J.M. Suijkerbuijk, Delphine Menard, Robert McLeary, Louise Johnson, Laura Fish, Sarah Ejiama, Berta Sanchez-Laorden, Juliane Hohloch, Neil Carragher, Kenneth Macleod, Garry Ashton, Anna A. Marusiak, Alberto Fusi, John Brognard, Margaret Frame, Paul Lorigan, Richard Marais, Caroline Springer

    Cancer Cell


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