14th International Medical Education Workshop on Molecular Targeted Therapy of Cancer (MTTC)
Vemurafenib and ipilimumab for metastatic melanoma
Dr Caroline Robert - Institute Gustave Roussy, Paris, France
It’s wonderful because melanoma was really a cancer that was extremely difficult to treat, I’m talking about the metastatic disease, and now for the last two years we have two new drugs on the market and they are in two different strategies. Now these two drugs, one is a BRAF inhibitor, vemurafenib, for BRAF mutated melanoma which is the case in about 50% of the disease, and the other one is ipilimumab, it’s an immunotherapy and it’s not restricted to BRAF mutated melanoma. So targeted agents, anti-BRAF, work in a lot of patients among the BRAF mutated melanoma; unfortunately most of the time the effects stop after some time, the progression free survival is around six months. And on the other side immunotherapy, it doesn’t really work in a lot of patients but it gives long term effects. So it’s a little bit of a mirror image, these two strategies. But the very good thing is that now in these two strategies we already have something which seems to be better for each of them, for the BRAF inhibitor for the patients with mutated melanoma it really seems we have very strong preliminary data that tell us that the combination of BRAF and MEK, of anti-BRAF plus anti-MEK agents, are going to be more powerful, more potent I mean, and with a longer effect on the patients. On the other hand in the field of immunotherapy we now have an anti-PD1 antibody and this immunotherapy has less adverse events that ipilimumab, works in more patients and also apparently gives long term effect. So you see we have two new agents, they are already challenged in their category by two new strategies and of course now we’ll try to combine these two strategies. So it’s a moving, moving field with a lot of hope. But we need to continue because right now for the patients it’s still difficult. So it’s very important that everybody understands that we are very happy that it finally moves and it progresses but we have to continue our efforts because on the side of the patients it’s still very difficult.
What would the combination therapy consist of?
The phase I trials already begin to explore these possibilities. So, unfortunately, the combination of vemurafenib, the first in line anti-BRAF agent, plus ipilimumab has been tried and the trial was interrupted because of toxicity, liver toxicity. But maybe it’s not the good news, maybe it’s the good design, and now of course we think very actively of combining anti-PD1 with targeted agents. So this is exactly the combination in the same patients or maybe a sequence, maybe it should not be at the same time, but we have a lot of designs to explore.
Is there anything else developing in the field of melanoma?
There are other immunotherapies that are evaluated but presently it’s really anti-PD1 or also anti-PDL1, maybe, targeting that really raises the biggest hope. Although we are going to hear at the next ASCO meeting, which is going to take place next month, we are going to hear about the results of the combination of anti-PD1 plus anti-CTLA4 which also might be very interesting.