How an Understanding of Melanoma Development is Changing the Clinical Landscape of its Treatment

Malignant melanoma is among the most serious skin cancers and its incidence has risen steadily in the past few decades

  • Date: 28 Sep 2014
  • Author: Evandro de Azambuja, Congress Daily Editor-in-Chief, Institut Jules Bordet, Brussels, Belgium
  • Topic: Melanoma and other skin tumours
Evandro de Azambuja

Evandro de Azambuja
Congress Daily Editor-in-Chief

Although outcomes are good for patients diagnosed with early stage disease, more advanced stage melanoma, including metastatic melanoma has a particularly poor prognosis. Sadly, while significant advances have been made in the treatment of other cancers, the same cannot be said for metastatic melanoma, and survival among patients is largely unchanged over the past 25 years. However, in recent years, we have seen advances in our understanding of the mechanisms involved in the development of melanoma and the involvement of the immune system in this process. This greater understanding has led to the identification of specific therapeutic targets for melanoma.

Marked improvements in outcomes have been seen over the last few years with the introduction of new treatments: ipilimumab, a human anti-CTLA-4 monoclonal antibody; trametinib, an inhibitor of the mitogen-activated protein kinase enzymes MEK1 and MEK2; and BRAF inhibitors, such as vemurafenib. These treatments have given rise to enhanced outcomes, thereby expanding the options for patients. However, despite the clinical benefits of these newer agents, they may not be suitable for all patients. It is clear that further treatment options are needed.

The profile of melanoma research is such that tomorrow’s Presidential Symposium (Monday 16.00 – 17.20, Madrid) is dedicated to research in this tumour type. Three late-breaking abstracts of data from phase III trials, and with practice-changing potential, will be presented. Prof Jeffrey Weber from the H. Lee Moffitt Cancer Cener Research Institute, Tampa, FL, USA will present results investigating the immune checkpoint inhibitor antibody, nivolumab, in patients with previously treated advanced melanoma, including those with ipilimumab-refractory disease ( LBA3_PR). Particularly exciting, I think, will be results from two studies comparing the use of first-line combined MEK and BRAF inhibition with BRAF inhibition alone in patients with tumours harbouring the BRAFV600E mutation. Results will be presented from two studies: one, from Dr Grant McArthur from the Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia investigating the addition of cobimetinib to vemurafenib ( LBA5_PR); and the other, reported by Dr Caroline Robert from the Institut Gustave  Roussy, Villejuif, France comparing dabrafenib plus trametinib with vemurafenib ( LBA4_PR).

The focus in recent years on new molecular targets that modify the development of melanoma has given rise to new and exciting advances that may pave the way for much-needed novel therapies. Yesterday, the results from studies of novel agents and combinations were revealed in a Proffered Paper Session. Encouraging results from an early-phase study were presented for the combination of LEE011, a novel cyclin-dependent kinase 4/6 (CDK 4/6) pathway inhibitor and LGX818, a novel BRAF inhibitor (1086O), while a phase I study showed promising findings for the combination of nivolumab and ipilimumab in the treatment of advanced melanoma ( 1085O). I anticipate that tomorrow’s Poster Discussion on Melanoma and Other Skin Tumours (Monday 13.00 – 14.00, Valencia) will expand our understanding of the impact that new and potential therapies have on the disease process itself on a molecular level and patient outcomes from a clinical perspective. For example, results will be presented on the genetic determinants of outcomes with specific therapies, such as ipilimumab ( 1090PD) and vemurafenib plus cobimetinib ( 1093PD). Survival and quality of life outcomes will also be presented for nivolumab ( 1088PD) and a dabrafenib/trametinib combination ( 1091PD). Of particular interest will be results with the MEK inhibitor, binimetinib ( LBA35), in patients with NRAS-mutated melanoma, a poorly studied group of patients.

I believe that the treatment of melanoma, particularly advanced disease, has come a long way in recent years. Focused research has been invaluable for increasing our understanding of disease development, which in turn is reaping rewards in terms of expanding the novel, targeted therapies available to us. Combining agents with potentially synergistic qualities, either sequentially or concomitantly, offers even greater possibilities for enhancing the benefit of these therapies. Results of studies presented at ESMO 2014 will help us to assess the clinical value of these new approaches for melanoma and may even have implications for other tumour types. The future treatment of patients with melanoma is looking promising.

I would like to thank the Editorial Team of Associate Editors Markus Joerger, Floriana Morgillo and Associate Guest Editor Giuseppe Curigliano for their assistance in producing the Congress Daily newspapers.