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Expert panel: Exciting new progresses for treating malignant melanoma

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MDFM INSIGHT Special Edition: January 7th, 2014

 

 

SARAH:

MD-FM, medical news from around the world. Here’s Peter Goodwin’s with a special Insight edition:

 

PETER:

Hello in this programme we report on exciting progress for treating malignant melanoma announced recently at the 2013 European Cancer Congress in Amsterdam.

 

For patients with advanced and metastatic melanoma the conference heard that new type of immunotherapy could extend survival greatly beyond what has been the norm, with a plateau in clinical trials appearing on the curves of overall survival, meaning that patients stay alive, year after year:

 

STEPHEN HODI 01

 “ Twenty to twenty two per cent of patients will continue to be alive from many months to many years afterwards. And then there’s this plateau, the survival seems to be quite durable at that point

 

DIRK SCHADENDORF 01

 “In the past patients treated with DTIC, our standard chemotherapy, died within ten months and long-term survival was an exception. Now we have a three-year survival rate of 22 per cent, and this 22 per cent survival after two years, is stable after five years, after seven years. So still more than 20 per cent of patients are surviving.

 

PETER:

That was Dirk Schadendorf from Essen in Germany and before him Stephen Hodi from Boston, USA, talking to MDFM about their research with ipilimumab, one of several new drugs that could change the game for patients with advanced melanoma.

 

Their study had the longest follow up of the largest group of patients receiving this CTLA-4 inhibiting monoclonal antibody. Results from 12 separate studies were pooled and between them a clear picture was emerging Dr Schadendorf told us: 

 

DIRK SCHADENDORF 02

 “We are moving to a clinical cure with a substantial fraction of patients are still free of disease more than five years”

 

STEPHEN HODI 02

 “That sub-set of 20 to 22 per cent of patients or so have long-term survival benefit from being treated with ipilimumab

 

PETER:

Stephen Hodi from the Dana-Farber Cancer Institute in Boston and, just before him, his co-researcher Dirk Schadendorf from Essen University. 

 

One study at the ECC 2013 meeting in Amsterdam looked at progression free survival as compared with overall survival. A contentious issue in many cancers is whether you can use PFS as a surrogate for overall survival: and Keith Flaherty came up with definite findings on this in the setting of melanoma:

 

KEITH FLAHERTY 01

“Basically, we took an aggregate of all the randomized trials that have been conducted with decarbazine as a control arm which really is, you can see that the therapy that stood as the standard comparator for about four decades, prior to the newer therapies which have finally broken to and become the new standard. And we wanted to ask the question: with the recent advances that have been made, with ipilimumab, debrafinib, demurafinib and trumatinib, so an immune therapy and three targeted therapies, each showing improvements in randomized trials. Could we start to try to make a relationship between progression free survival and overall survival when considering not only these positive studies, but also the negative studies as well.

 

PETER:

And Dr Flaherty told us this was all good news for investigators looking at new therapies for melanoma:

 

KEITH FLAHERTY 02

 “What we found was a very robust relationship between PFS and OS. Highly statistically significant relationship, in using a correlation coefficient which would suggest no relationship as zero, and a relationship of 1.0 being perfect. We observed relationships between 0.85 and point nine five

 

 

PETER:

Keith Flaherty from the Massachusetts General Hospital in Boston.

 

Also at the Amsterdam conference there were other studies signalling a sea-change in treatments for melanoma.

 

One of these reported a doubling of five year overall survival in patients randomised to treatment with ipilimumab added to their standard dacarbazine thereapy. And investigator Michele Maio from Siena in Italy told us there was more good news:

 

MICHELE MAIO 01

 “We have confirmed, further confirmed, that if patients lets say make it to the third year of their disease, then the chance of dying of their melanoma decreases dramatically. So there is a plateau that occurs from the third year on. So this means clearly that we have something that works in the long range for our patents.

 

PETER:

Dr Maio explained that ipilimumab’s immunological mode of action was complementary to the mechanisms of other important new agents also showing great promise in advanced melanoma:

 

MICHELE MAIO 02

 “Ipilimumab has to modulate or to activate the immune system so it takes time in order to work. Other agents like birafinib inhibitors the mek-inhibitors, they act directly at tumour sight and they can be utilised in a large proportion of our patients who bare a specific mutation of their DNA. I don’t think the two agents or the two strategies are alternative to each other, I think that we have two important ways to treat our patients, and the future will definitely be how to combine these agents or how to sequence these agents in order to improve significantly the long term survival of our metastatic melanoma patients.”

 

PETER:

So there’s scope for more progress against melanoma using the new agents we already have at our disposal, and plenty of scope for finding yet more anti-melanoma drugs:

Keith Flaherty told MDFM his data on progression free survival has important implications for the longer term:

 

KEITH FLAHERTY  03

 “You’d say that overall survival of course has been what we’ve been shooting for for a long time. Now that we’ve documented it and I think emphatically so when you look at the long-term follow-up data that was presented in Dr Maio and Dr Hodi’s presentations today, you’d ask the question, can we predict any of that with end points that can be achieved even within the first six months or so of a clinical trial. And this data suggests in fact that you can, that if you observe an impact on progression free survival in a randomised trial, highly likely that that’s going to translate into an overall survival benefit”

 

 

MICHELE MAIO 03

 “I think it’s encouraging to start learning that PFS the progression free survival can be a good surrogate for overall survival because this will mean that we will shorten the time of our studies and observations and also that we will have the possibility to learn more whether a specific agent improved the survival

 

PETER:

Michele Maio and before him Keith Flaherty, who gave us his thoughts about the implications for patients of the findings we’d all been hearing about at the Amsterdam conference:

 

KEITH  FLAHERTY 04

“Those who maintain a response beyond the second or third year of initiating treatment, seem to be essentially cured of disease in terms of the absence of melanoma related deaths thereafter and that I think is a profound statement when you consider that complete radiographic responses happen quite infrequently

 

PETER:

Keith Flaherty from Boston.

 

And Professor Cora Sternberg from the San Camillo and Forlanini Hospitals in Rome chaired a press briefing dealing with some of the new data.  What did she make of these developments?

 

CORA STERNBERG 01

 “This is the longest that we’ve seen patients living and I think that this is very big and important news and its very important for patients. Patients are living longer and that’s what they want to know and that’s what needs to come out of this message of this is that, patients are living longer with the new immunologic therapy like anti-CTLA-4, ipilumumab and with other new melanoma therapies, patients are living longer and that’s what patients need to know

 

PETER:

Cora Sternberg from Rome.

 

PETER:

And that winds up this MDFM Insight edition devoted to some of the recent big progress in treating meatastatic melanoma reported at the 2013 European Cancer Congress held in Amsterdam. More from us soon, but for now from me Peter Goodwin, good-bye!

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