More therapeutic options for metastatic melanoma patients

At the 2014 European Society for Medical Oncology congress in Madrid, Spain, a set of studies focusing on metastatic melanoma were presented. The scientists’ goal was to help patients manage relapse and overcome cancer’s resistance to treatment.

Our Chief Medical Officer reports the latest developments.


Superior treatment for relapsed metastatic melanoma

Among the treatments for patients with metastatic melanoma is the drug ipilimumab or a set of agents known as B-RAF inhibitors. In some of the patients receiving these treatments, cancer may relapse, and they will need what is called a “second line treatment”.

In a recent study [1], a drug called nivolumab was tested. Nivolumab is scientifically described as a “PD-1 inhibitor”, and acts to block the mechanisms for disease progression. 

This drug was compared against chemotherapy (with the agents carboplatin & decarbazine) in a trial with patients with cancer having the characteristics described above. The results of the trial showed that nivolumab was superior, as 32% of the patients responded. Furthermore, the side effects were acceptable, meaning that the impact in the quality of life of these patients was not adverse.


Overcoming cancer resistance to drugs for advanced melanoma

Patients with metastatic melanoma treated with vemurafenib and dabrafenib (scientifically known as B-RAF inhibitors) can have good results. However, after a few months of treatment, resistance to the drugs develops, which makes them less effective.

This resistance is partially related to a phenomenon scientifically described as “over-expression of the MEK pathway”. Inhibitors of this pathway act in such a way to overcome this resistance and make cancer more responsive to the treatment.

In their search for new, better treatments compared to this standard combination of vemurafenib and dabrafenib, researchers tested 2 new combinations on two separate studies [2, 3]:

  1. vemurafenib and cobimetinib
  2. dabrafenib and trametinib

Both combinations were proven superior compared to the standard combination of vemurafenib and dabrafenib. In particular:

  1. cancer was more responsive to treatment, and
  2. the period without progression of melanoma was longer.



  1. ESMO abstract: LBA3_PR - A phase 3 randomized, open-label study of nivolumab (anti-PD-1; BMS-936558; ONO-4538) versus investigator's choice chemotherapy (ICC) in patients with advanced melanoma after prior anti-CTLA-4 therapy: J. Weber (Tampa, United States of America)  D. Minor (San Francisco, United States of America)  S. D'Angelo (New York, United States of America) F. Hodi (Boston, United States of America)  R. Gutzmer (Hannover, Germany)  B. Neyns (Brussels, Belgium)  C. Hoeller (Vienna, Austria) N. Khushalani (Buffalo, United States of America)  W. Miller (Montreal, Canada)  J. Grob (Marseille, France)  C. Lao (Ann Arbor, United States of America) G. Linette (St. Louis, United States of America)  K. Grossmann (Salt Lake City, United States of America)  J. Hassel (Heidelberg, Germany) P. Lorigan (Manchester, United Kingdom)  M. Maio (Siena, Italy)  M. Sznol (New Haven, United States of America)  A. Lambert (Braine-l’Alleud, Belgium) A. Yang (Princeton, United States of America)  J. Larkin (London, United Kingdom)
  2. ESMO abstract: LBA4_PR - COMBI-v: A randomised, open-label, phase III study comparing the combination of dabrafenib (D) and trametinib (T) with vemurafenib (V) as first-line therapy in patients (pts) with unresectable or metastatic BRAF V600E/K mutation-positive cutaneous melanoma: C. Robert (Villejuif Paris, France)  B. Karaszewska (Konin, Poland)  J. Schachter (Ramat-Gan, Israel)  P. Rutkowski (Warsaw, Poland) A. Mackiewicz (Poznan, Poland)  D. Stroyakovskiy (Moscow, Russian Federation)  M. Lichinitser (Moscow, Russian Federation) R. Dummer (Zürich, Switzerland)  F. Grange (Reims, France)  L. Mortier (Reims Cedex, France)  V. Chiarion-Sileni (Padova, Italy) K. Drucis (Gdansk, Poland)  I. Krajsova (Prague, Czech Republic)  A. Hauschild (Kiel, Germany)  P. Sun (Collegeville, United States of America) S. Rubin (Collegeville, United States of America)  J. Legos (Collegeville, United States of America)  W. Crist (Collegeville, United States of America) S. Little (Collegeville, United States of America)  D. Schadendorf (Essen, Germany)
  3. ESMO abstract: LBA5_PR - Phase 3, double-Blind, placebo-controlled study of vemurafenib versus vemurafenib + cobimetinib in previously untreated BRAFV600 mutation-positive patients with unresectable locally advanced or metastatic melanoma (NCT01689519). G. McArthur (East Melbourne, Australia)  P. Ascierto (Napoli, Italy)  J. Larkin (London, United Kingdom)  A. Ribas (Los Angeles, United States of America) G. Liszkay (Budapest, Hungary)  M. Maio (Siena, Italy)  M. Mandalà (Bergamo, Italy)  L. Demidov (Moscow, Russian Federation) D. Stroyakovsky (Istra, Russian Federation)  L. Thomas (Rhone, France)  L. De La Cruz Merino (Sevilla, Spain)  V. Atkinson (Woolloongabba, Australia) C. Dutriaux (Bordeaux, France)  C. Garbe (Tubingen, Germany)  I. Chang (South San Francisco, United States of America) S. Hack (South San Francisco, United States of America)  B. Dréno (Nantes, France)

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