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Posts tagged ‘ESMO 2014 Cobimetinib’

ESMO 2014, the Congress of the European Society for Medical Oncology takes place in Madrid next month. Yesterday on Twitter, it was announced that the late breaking abstract titles had been added to the searchable online program.

Late breakers, by definition, provide an opportunity for the most recent data to be presented. Over the next few posts we’ll start to look at the forthcoming program and the late breakers that have been announced.

Obviously until the abstracts are published there’s no data to discuss, but nonetheless the titles give an indication of what may be hot news at the Congress.

For those going to the ESMO 2014 “searchable” online program, be warned it’s not the most user friendly of search engines.

At large scientific and medical meetings, a lot of sessions run in parallel, it’s the only way to get through the volume of data in a few days, and most clinicians tend to be sub-specialists. The plenary, or Presidential session, as its known at ESMO 2014 is the rare opportunity where all congress attendees get together to hear what the organizers think is the most noteworthy, compelling or practice-changing data at the meeting.

Unfortunately, the trend at recent meetings has to been to focus on data from large phase III trials, and indeed at ASCO the plenary featured negative breast cancer data. While we believe that negative data should be presented, since it is particularly informative to those in that specialist area, plenary sessions should ideally have data that make you sit up and think, ‘Wow!’

The American Society of Hematology (ASH) missed the opportunity at their 2013 annual meeting to provide a plenary on chimeric antigen receptor based T cell (CAR-T) therapy, which looks likely to revolutionize hematology. The Novartis/UPenn CTL019 data for the treatment of children with acute lymphocytic leukemia (ALL) was stunning. Readers may recall that Gleevec obtained a plenary at ASH back in 1999 on the basis of dramatic phase I data so a precedent has been set, even if it has not been followed much since then.

At ASCO this year, the compelling data in immuno-oncology, particularly for the treatment of metastatic melanoma by PD-1 inhibitors nivolumab and pembrolizumab and the anti-PD-L1, MPDL3280A, in bladder cancer were particularly noteworthy, and would not have been out of place in a plenary session.

It’s disappointing sometimes to see the committees that vote and decide on which abstracts merit a plenary seem to be traditionalists and not to be on top of immuno-oncology and immunotherapy, where the practice changing data is emerging.  At the current rate, some of these agents are highly likely to be approved by the FDA before they make it to prime time consideration at a cancer conference, which is very strange indeed.

With this in mind, let’s take a look at what ESMO chosen for their two Presidential sessions in Madrid. Subscribers can login to read more, or you can purchase access below.

At the annual AACR meeting last year, I wrote about an awesome piece of research from Meghna Das (NIBR) who looked at intermittent dosing of vemurafenib in animal models of BRAF driven melanoma and found that such an approach reduced resistance and improved outcomes.

GarrawayLeviMany of us are unlikely to forget the fascinating sequence of photos shown by Levi Garraway (Broad/MIT) two years earlier at the same conference, when he highlighted the before and after impact of vemurafenib therapy on a patient with advanced melanoma in glorious technicolour. Sadly, the subsequent photo six to nine months later showed that the lesions came back with a vengeance and the patient passed away.

Given that the disease is exquisitely sensitive to BRAF inhibitors, how can we improve this situation and overcome the resistance for future patients?

Das’s work was one of the highlights of that conference for me, since it involved creative thinking and a series of very well done, logical experiments that clearly showed an impact. The post drew a lot of ire and attention though, with many researchers emailing me to say they thought the idea was crazy and utterly against their understanding that you need to continually hit the target 24/7 or risk sudden relapse.  It drew as much surprised reaction as a related and controversial post on minimally effective dose, where I argued that we needed new approaches to hitting the target.

Today, it’s time for an update on this controversy – what happens when we go from bench to bedside and back again? What can we learn from an N of one that helps us figure out the optimal strategies for overcoming acquired resistance to TKI therapy?

Therapies mentioned: vemurafenib, dabrafenib, trametinib, cobimetinib

Companies mentioned: Roche/Genentech, Novartis, GSK, Exelixis

The story is truly a fascinating one – sign in or sign up below to learn the latest developments in BRAF-driven malignancies.

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