A Remarkable Colorectal Cancer Immunotherapy Meeting
As my most recent Currently Incurable Scientist column began: On December 2, 2015 a remarkable meeting took place. Jointly organized by Fight Colorectal Cancer (Fight CRC) and the leading immuno-oncology organization the Cancer Research Institute (CRI), an unprecedented meeting gathered many of the world’s leading experts on both CRC and immuno-oncology. Top scientists devoted to CRC research sat around the same table together for the first time to discuss what is needed to advance immunotherapy for CRC.
This meeting was both unprecedented and I believe absolutely necessary for the CRC patient community – so I wanted to present here in my personal blog a few Director’s Cut bonus features, trying to explain the viewpoint of the meeting from both a scientist’s as well as a currently incurable patient’s eyes.
Who was there? Leading experts in both CRC & immuno-oncology, from both public and private institutions: Dr. Al Benson (Northwestern U), Dr. Emily Chan (Vanderbilt U), Dr. Dustin Deming (U of WI) Dr. Luis Diaz (Johns Hopkins), Dr. Wolf Fridman (INSERM), Dr. Franck Housseau (Johns Hopkins), Dr. S. Peter Kang (Merck), Dr. Smitha Krishnamurth (Case Western U), Dr. Dung T Le (Johns Hopkins), Dr. Wells Messersmith (U of CO), Dr. Cynthia L. Sears (Johns Hopkins), Dr. Neil Segal (Memorial Sloan Kettering Cancer Center), Dr. Arvin Yang (Bristol-Myers Squibb), Dr. Rebecca Moss (Bristol-Myers Squibb), Dr. Edward Cha (Genentech), Dr. Tom Dubensky (Aduro Biotech), and Dr. Dirk Brockstedt (Aduro Biotech) as well as representatives from both Fight CRC and the Cancer Research Institute.
I was thrilled and grateful to be involved with this meeting via both my close partnership with Fight CRC as well as my growing relationship with the Cancer Research Institute – a relationship which now includes my first opportunity to write for an immuno-oncology website as well as becoming the Cancer Research Institute’s “immunoadvocate” for colorectal cancer. As a strong proponent of immunotherapies, being both their immunoadvocate and a part of this meeting was a scientific dream come true!
Why This Kind of Meeting is Important and Exciting
There are many benefits to bringing together experts for this kind of focused discussion. Science, especially immuno-oncology, is incredibly complex. Attacking this kind of scientific problem has the greatest chance of success when the latest information and ideas are discussed in person by experts in a collaborative environment. They can exchange the latest knowledge from their respective studies in a dynamic conversation format. They can focus attention on key scientific unknowns still unanswered. They can brainstorm new ideas and approaches. They can explore new joint strategies. This meeting was intended to foster exactly those goals, to push the science forward. To push the field closer to a cure.
The Big Goal
Was the meeting intended to announce a major research breakthrough that immediately solves the non-MSI CRC immunotherapy issue? No, it was not.
Instead: This panel of experts came together from academia and industry with this BIG GOAL on their plate: determining the blueprint needed to better understand the science of CRC immunotherapy in order to ultimately maximize its potential to treat ALL forms of CRC.
As I wrote about previously, there are already strong preliminary signs that the “microsatellite instable” (MSI-high) subtype of CRC is responding to anti-PD-1 immunotherapy. Since I wrote that column, the PD-1 inhibitor pembrolizumab (Keytruda™) has been granted a “breakthrough drug designation” by the FDA in order to accelerate its development for MSI-high CRC. Although this is a fantastic development for the MSI-high sub-type of CRC, unfortunately most people diagnosed with CRC are non-MSI.
Non-MSI CRC has proven to be more resistant to treatment by immunotherapies.
The key question is why?
You can’t answer a scientific problem rationally unless you first truly know the question(s) that are needed to be answered in order to move a field forward & achieve the BIG GOAL. Thus, trying to answer that “why question” was a focus of the experts’ discussion. The question can (and needs to) be asked from a number of different ways:
- What are the key reasons why MSI-high CRC responds to anti-PD-1 therapies?
- What are the key reasons why non-MSI CRC is resistant?
- Are there outlier patients whose study can give clues on new successful therapeutic strategies?
- Are there therapies that could be used to make non-MSI CRC “look like” MSI-high CRC and become responsive to anti-PD-1 therapies?
- Are there non-PD-1 based immunotherapy strategies which may be more appropriate for non-MSI CRC?
The Non-MSI CRC Patient Population is Crying for Help
There is a sense of urgency in the Stage IV CRC patient population. I share it – we all do – for very obvious reasons. In my observation, this sense of urgency is even higher in the non-MSI patient population. This sense of so far unanswered non-MSI urgency leads to frustration. Due to the high stakes and pressure involved, this frustration at times can boil over into anger.
After seeing the preliminary signs of success in MSI-high clinical trials and the ensuing explosion in MSI-high follow-up clinical trials, I can sense a very real feeling of worry (panic for some?) within the non-MSI patient population that they are not a focus of immunotherapy research now that MSI-high CRC is achieving so much immunotherapy success. I believe this worry is unfounded. A goal I have for this roundtable is to show to the non-MSI patient population that yes – scientists know how urgently they are in need of new therapies and yes, they are working hard on the non-MSI CRC immunotherapy problem!
As a patient keeping an eye on the game clock, I struggle with the pace of science. As a scientist, I know that the issues being addressed are very complex (although I firmly believe solvable). Solving complex problems takes time and a lot of hard work. It just does. If it were something comparatively simple like flying to the moon, curing CRC would have been done over 40 years ago… But I do firmly believe that after decades of conceptual hope, our cure/long term disease control spaceship is now finally on the launch pad and we have entered the final countdown. Hopefully the countdown isn’t paused too many times before the clock finally hits zero! I love the symbolism of this Apollo Saturn rocket photo because it was surrounded by darkness with just a glimmer of hopeful light in a small piece of the sky – as the rocket was lit up with flood lights below in anticipation of a successful launch when its time comes.
The December 2nd meeting was only the start of this collaboration of experts. As I mentioned, the science of immuno-oncology is incredibly complex. A 1-Day discussion will not answer all the scientific questions but it is a necessary first step for success. The panel of experts will continue to further discuss the latest scientific information and strategies – with (it bears repeating) a singular goal in mind: to develop a blueprint to better understand the science of immunotherapy in CRC treatment, in order to ultimately maximize its potential to treat ALL forms of CRC.
AS SOON AS POSSIBLE.