Surfing the AACR Waves of Science
Surfing the AACR Waves of Science
What a day. I just woke up from a drug-induced nap that wasn’t particularly long but it was deep. For the second FOLFIRI chemo infusion in a row, I fell into such a deep sleep when I got home, that when I woke up it felt like I had slept for many hours. Looking over at the clock, it said 4:37. That felt about right – a good 13 hours of deep sleep was exactly what I needed! Wait. The sun was shining brightly??? Uh oh – I must have been just knocked out for about an hour. Oops. Thank you for passing me out Ativan (Lorazepam) – but a bigger thanks for letting me forget about my nausea as much as possible! Feeling nauseous, I wish I could sleep another 12 hours but I don’t think that is in the cards I’m being dealt. Steroids and sleep don’t play well together.
At least I caught it earlier this time. Two weeks ago after infusion, the same black-out happened but that time I woke up at 7:15 PM. With the level of light at 7:15 AM & PM somewhat similar that close to the spring equinox I jumped in the shower, ran into the kitchen to make some quick coffee and asked why the girls weren’t ready for school yet? We’d be late! Oh, it’s 8 PM. Oops. I’ll go back to my chemo sleepy-bed again… sorry family… Dad hasn’t gone entirely insane…
Backtracking a Few Days… What an Exhilarating Week to be a CRC Patient-Scientist
Science is continuously being worked on and advancing but due to both chance quirks as well as organizing events like the AACR meeting – there a bursts of scientific progress and activity. For CRC, it felt like one of those weeks this past week.
It all started with the publication of a groundbreaking new paper “Genomic Correlates of Immune-Cell Infiltrates in Colorectal Carcinoma”. A tongue twister I know but it truly was a tour-de-force paper from the Broad Institute and partners which, in the grandest scope ever done in CRC research thus far, examined many hundreds of CRC samples going back to the 1970’s using detailed genetics as well as immune system interactions. What they obtained was the clearest picture yet of CRC at the genetic level as well as its detailed interactions with (and some novel ways it avoids) the immune system. This is all incredibly important data to have in this time period of targeted therapies and CRC immunotherapies. My hats off to them for a masterful study!
With 2016 Technology It’s Easy to Not be Alone
It turns out that although I did not know the lead author of the above publication, I have recently become friends with Dr. Corrie Painter at the Broad Institute. Now I am going to wait until I write a focused post on just her and her projects to go over her accomplishments, in order to do her story justice. At the very broadest level: she is simply the most amazing Stage IV patient-scientist-advocate I have ever met! Shuffling back and forth between those three roles (sound familiar?) she is doing AMAZING things in the worlds of angiosarcoma and breast cancer – things that are & will change the world. She makes my patient-scientist-advocate activities look like child’s play hobbies! She really is that good – but it is always good for me to have a role model & inspiration! The best part is that she is totally cool and I was chatting with her on Twitter a few days ago and I mentioned how great the new CRC paper was.
Awhile later this picture was tweeted to me. It was Corrie and the first author of that groundbreaking CRC paper Marios swinging by to give me a “virtual hi”. How cool is that?
It really is amazing how technology like Twitter and Facebook have brought people together – not only on the social & patient support level but on the scientific and advocate levels as well. Not just with Twitter photo “author Hi’s” to accompany my reading of a landmark paper trying to help cure my own disease. But also with the recent drawing together of ever closer scientist and advocate acquaintances from Argentina, England, Israel, Russia, China and most recently the Czech Republic. All brought together by CRC, all brought together by common causes and social networking technology.
In the midst of a difficult chemo day today, by chance it was the annual American Association for Cancer Research (AACR) meeting. The AACR is an incredibly large and important meeting which spans the top quality of oncology research from the most basic research, to translational research to the clinic, to clinical and population data itself. I’ve been to it a number of times and its sheer size, scope and quality leaves you breathless as you walk around. I was given an opportunity to fly there by Fight Colorectal Cancer (CRC) to help them in the scientific interpretation & reporting of sessions. I would have loved to go but the logistics in the middle of FOLFIRI treatment and other trips were simply too much to handle this year – maybe next year! 🙂 Enter the incredible power of 2016 technology
The CRC Immunotherapy Blueprint
It was in particular an extra special AACR meeting this year for Fight CRC because it was going to be the public release of the CRC Immunotherapy Blueprint developed by an expert roundtable who had been organized by them and the leading immunotherapy organization the Cancer Research Institute (CRI). It was the culmination of months of work of a group of the world’s leading experts on GI oncology and immunotherapies. A group I was proud and excited to play a role in. The blue print was presented at the AACR today along with this brief summary I helped write. A full scientific paper outlining the blueprint will be published shortly!
The summary was being finalized as my anticipatory nausea started to build… All of my portion of the work could be done from afar, between my word processor, Facebook and Twitter accounts – even as the anticipatory nausea started to build ever stronger. A strange dichotomy between working towards grand goals and feeling so bad I just wanted to roll up into the fetal position began to develop. But that is not a convenient way to type, so I forced myself to stay in my writer’s position. A small gesture but one that shows, on a very specific & personal level, how my writing helps me in my disease. Rumor has it that laying in the fetal position in the afternoon is not good for one’s health – metal, emotional or physical. ha
I just kept telling myself that this is why we are pushing immunotherapies so hard. So future CRC patients never have to feel this sick dichotomy ever again.
Chemo days are strange days. I had written about them once before, actually one of my very first posts. At that time I was taking “chemo-light” (5-FU + Avastin). Those chemo days were a piece of cake! As witnessed last Fall between my reluctance to restart FOLFIRI and even a subsequent Emergency Room trip due to pain (that I don’t think I ever bothered blogged about), FOLFIRI is an entirely different beast. It is the farthest thing from a piece of cake. It takes over both your and your family’s lives. The girls have done a remarkable job of adjusting to Daddy’s “sleepy medicine days” I am very proud of them 🙂 I am hoping that as they get older they will learn more fully the life lesson of fighting against all odds for what you believe in. Fighting for your children, even when it is rough to do this on many different levels.
What Made Today Such an Incredible and Exhilarating Experience
Starting the day before chemo, the AACR was an incredible experience to behold. I experienced it in an entirely new way this year fueled by Twitter. Monday morning I signed in as @CurrentIncurSci and started to build up key people in attendance to follow. Building a virtual attendee list on Twitter. I wanted to know data ASAP, lives of friends of mine could depend on the speed. I could watch video replays at work a few weeks from now – but in some of my Stage IV friends’ lives – “a few weeks” is a significant proportion of their prognosis… I set my corner of the Twitterverse to look at AACR and I laid back to watch the results stream in to my computer. Cell phone photos of slides, cell phone photos of posters, links to papers, commentary by people that know a lot more about some targets than I do... In my pre-chemo nausea I just sat back and absorbed, downloading pictures as needed for permanent filing.
It was not simply exhilarating seeing the rush of data scroll in almost in ala the Matrix – it was exhilarating because some of it was high impact on CRC. On my disease. On the disease of many of my closest friends! The twitter feed slowed down to a crawl on Monday night. I was also slowing down to a crawl as the nausea built.
There were some very important planned CRC talks on Tuesday. My infusion day. This is tricky because to “tolerate” (I love that “oncologist phrase”) FOLFIRI, I need to take high dose Ativan which first makes me drunk as a skunk and then I get knocked out. Yes I take Uber or a taxi home! What did I do? While I have become acquaintances and friends with a number of people around the Twitterverse that are just as interested in potential cures as I am. I asked them to stand in for me and to send me any CRC posts that came up. I was very touched when they agreed – these are people I know from a purely electronic twitter handle and often for not very long – but even in 21st century, basic humanity shines forth.
Being Driven Awake
So that was the plan. But what happened? For the first time I stayed fully awake during FOLFIRI infusion due to the sheer thrill of the watching immunotherapy and CRC news being released in continuous real time! No home runs for CRC… but YES finally signs that things really are starting to come together for MSS-CRC which has lagged behind some other tumor types. It is hard, even for Ativan, to knock a patient-scientist-advocate out when data that could lead us closer to cure for me and all my friends is being presented as we speak!
A Few CRC Items of note from AACR-2016
Keep in mind this is in no way even close to listing ALL the major CRC news from AACR this week. Even if I wrote any entire post on that, it would be difficult to accomplish and not miss great science. Science is moving SO fast right now – although I know we always want it to move faster! I want my brief mentions of these few items to illustrate how quickly CRC therapies are moving! And I will keep it brief just so this doesn’t turn into my first book instead of a blog post!
Some Therapeutic Highlights that Caught My Eye
- Labetuzumab govitecan (IMMU-130), an anti-CEACAM5/SN-38 antibody-drug conjugate
- Immu-130 is an “Antibody-Drug Conjugate (ADC)”. In its presentation they showed significant activity in multiple patients who had previously failed irinotecan (a drug I took today!) with an improved side effect profile! An example of the power of targeting a drug with toxicities selectively to tissues via an antibody! It’s currently accruing trial is NCT01605318.
- Clinical activity and immune correlates from a phase Ib study evaluating atezolizumab (anti-PDL1) in combination with FOLFOX and bevacizumab (anti-VEGF) in metastatic colorectal carcinoma
- This trial combined a miracle PD-L1 inhibitor immunotherapy called “atezolizumab” along with standard of care chemo (FOLFOX) and bevacizumab (Avastin). The theory: Avastin has general immunostimuatory effects. The oxaliplain in FOLFOX causes cells to die in such as way that it essentially generates a mini-vaccination for the immune system to see. The atezo then comes in, removes the brakes from the immune system and it starts attacking the tumor
- The scientists running this trial did something bold. It was as “All-Comers” trial which means that any person with Stage IV CRC could be a part of the trial, as long as they met the other requirements. Note: I did not say “MSI-high”. As you know, MSI-high CRC patients are the ones currently published to show strong responses to immunotherapies so far. They are only 4% of the Stage IV CRC population however. In a relatively small trial like this one… by quirk of luck, this trial could theoretically end up with zero MSI-high patients in it, Like I said… bold. BUT BOLD TIMES REQUIRE BOLD SCIENCE.
- The results are pasted below. Not a home run but definitely signs of increased immune infiltration into the tumors (removing their romulanesque cloaking device) and potentially increased progression-free survival curves.
AACR National Meeting #2651, Wallin, J.J. et al (2016)
This trial has been going on long enough I hope they will present & publish a more comprehensive analysis of the data as soon as possible! It’s currently accruing trial is NCT# is NCT01633970.
- HUMAN TCRS for KRAS-G12D and KRAS-G12V
- A poster was presented by Wang et al from the NCI disclosing human TCR cellular immunotherapies targeting the KRAS-G12D and KRAS-G12V mutations which are very common in CRC and Pancreatic Cancer. These are basically off-the-shelf versions of the NIH TIL Clinical trial that I had tried to get into last Fall but failed due to surgical inaccessibility. The TCRs remove those stringent surgical requirements. (Although I personally can’t use these TCRs because I am KRAS-wildtype). Their HLA-Type is HLA-A1101. Didn’t I promise you a few months ago that these types of cellular therapies would steadily become more and more accessible to larger numbers of CRC patients? Welcome to the next BIG step in that process – with more to steps come!
- Study of Atezolizumab in Combination With Cobimetinib in Participants With Locally Advanced or Metastatic Solid Tumors (Finally a brief preview of ASCO-2016)
- To add to the excitement of today, it was announced (on Twitter no less)! That a major MSS-CRC co-therapy trial will be releasing data in early June at ASCO. I was so glad to see this because this is probably in the top-five of my current favorite trials – adding in a co-therapy (cobimetinib – a MEK inhibitor) to Atezolizumab to try to bring immunotherapy success to MSS-CRC. I’ll wait to a later post to explain the mechanistic details. This trial is currently accruing NCT01988896.
The entire MSS-CRC community has been anxiously awaiting results to start being released from many immunotherapy trials going on. The 2016 AACR and ASCO conferences will release the first. We’re realistic – we know most trails fail BUT… as PATIENTS – all we need is ONE to truly succeed to either cure us of the disease or prolong our life long enough to make it to the next even better trial. That is why we watch every trial release with held breath. OUR LIVES DEPEND ON THEM!
So there I was in the infusion chair. Physically not doing well… but how can I explain this… also excited beyond belief? It was perfect timing to have an infusion during the AACR meeting! The constant flow of information – as I struggled with the major issues of the standard of care drugs currently available to me and my friends – gave me a drive to identify things in today’s Twitter feed which would be better. More active. Less side effects. Therapies which instead of making you want to curl up into a ball – make you feel alive.
Today accomplished that, I was in my Matrix moment throughout the infusion – filled not with depression or a sense of defeat. But instead with a feeling of Hope and Excitement for what the future holds for me and as many of my friends as possible.
Surfing a constant wave of ground-breaking science was just what the Doctor ordered.
It was a perfect infusion day