The Colon Club

Brian:

I did not change my diet at all. (Though I am not the healthiest eater.)
My Mutations are:

KRAS G12A
AURKA amplification
APC E1379
ARFRP1 amplification
BCL2L1 amplification-equivocal
FANCG E105
GABRA6 K173T
GNAS amplification
SRC amplification-equivocal
TOP1 amplification
TP53 R175H
ZNF217 amplification

Microsatellite stable

Jack&KatiesMommy wrote:Brian:

I did not change my diet at all. (Though I am not the healthiest eater.)
My Mutations are:

KRAS G12A
AURKA amplification
APC E1379
ARFRP1 amplification
BCL2L1 amplification-equivocal
FANCG E105
GABRA6 K173T
GNAS amplification
SRC amplification-equivocal
TOP1 amplification
TP53 R175H
ZNF217 amplification

Microsatellite stable

Cynthia-
I have 8 of the same mutations. I find that crazy! May I ask- who is your oncologist?
Thank you & congrats!

My oncologist:

https://health.usnews.com/doctors/jeffr ... sen-669152

https://www.google.com/amp/s/amp.chilli ... p/87285454

Keytruda side effects? At least the ones you saw?

Pyro wrote:Keytruda side effects? At least the ones you saw?

Sorry! I just saw your post. The only side effects I have had vary each treatment that I have. (I have had 12 treatments so far) and some treatment cycles I noticed nothing! Other treatment cycles I had some pretty bad fatigue (I work 40+ hours a week as a lawyer and am very active with my two children, and do all fo the shopping, cooking, etc. for ur family...so fatigue is relative.). For a few of the treatment cycles I felt like I was stating to get the flu (chills and aches etc.) but it never developed into the flu and just went away....so I know it was the Keytruda. Other than these, I have had no side effects....though I have found myself with a very very unusually short temper and irritated with my family which I had never felt before. I don't know if this is related to the Keytruda or something else.

I came back to this thread and double checked my husband's TMB. I was off earlier. It's 7.605. I have no idea if that's considered low or intermediate/moderate.

mpbser wrote:I came back to this thread and double checked my husband's TMB. I was off earlier. It's 7.605. I have no idea if that's considered low or intermediate/moderate.

I am not sure about that.

I posted this is the DK37 Science Posts topic but I thought everyone here might find this information useful.

OK - I know plenty of you have an interest in MSI, MSS and TMB with regards to Immunotherapy agent usage. There have been a number of studies publish in the last year or so, but I have found the following ones to be quite interesting, and I am hopeful that before long more people will have their tumors profiled for TMB (Tumor Mutation Burden). The first paper is the following:

https://www.nature.com/articles/s41588-018-0312-8

Unfortunately I don't have a subscription to this journal so I can't access the paper at this time directly. Perhaps if I make a trip to the university I can get a copy of the paper. However - The following link I feel does a very good job of reporting the results of the above paper very well.

https://www.ajmc.com/newsroom/tumor-mut ... unotherapy

In these paper they point out different solid tumor types have different TMB cutoff levels where Immunotherapy drugs have a significant benefit. For Colon Cancer they indicate a TMB of about 52. But I suspect there are exceptions where lower than this immunotherapy is still useful. The following paper is also quite interesting.

https://bmcimmunol.biomedcentral.com/ar ... 018-0285-5

It is quite detailed. Note all these papers I presented so far concern overall TMB for multiple tumor types. Thing is most of the data so far has been for Melanoma and NSCLC where these immunotherapy drugs have been approved the longest and the vast majority of patients have come from. So its probably a bit biased towards the TMB numbers associated with these tumor types.

Here is a citation just concerned with Colon Cancer MSI, MSS and TMB

https://europepmc.org/abstract/med/30638897

Again I am sorry I don't have access to the last one directly either, but hopefully can get to a major research library sometime soon to read it. These are all very recent research publications. (Jan 2019) Hope everyone considering use of one of the immunotherapy drugs has a look, and armed with this new data perhaps can talk their oncologist into doing appropriate testing and consider these new treatments.

Regards,

GrouseMan

I have had a TMB test recently, and the number is 10.24. My onc. says my TMB is very high among the MSS patients. He will put me on Keytruda or Opdiva. The timeline is: I will have a CT scan; if Images show there is tumor growth, I will start immunotherapy. If disease is stable, I will continue current treatment.

Jack&KatiesMommy wrote:

Pyro wrote:Keytruda side effects? At least the ones you saw?

Sorry! I just saw your post. The only side effects I have had vary each treatment that I have. (I have had 12 treatments so far) and some treatment cycles I noticed nothing! Other treatment cycles I had some pretty bad fatigue (I work 40+ hours a week as a lawyer and am very active with my two children, and do all fo the shopping, cooking, etc. for ur family...so fatigue is relative.). For a few of the treatment cycles I felt like I was stating to get the flu (chills and aches etc.) but it never developed into the flu and just went away....so I know it was the Keytruda. Other than these, I have had no side effects....though I have found myself with a very very unusually short temper and irritated with my family which I had never felt before. I don't know if this is related to the Keytruda or something else.

Thanks, just realized you posted this already, sorry. I’m irritated on FOLFURI, hopefully it isn’t worse!

Hi Cynthia,

Thank you SO MUCH for posting your story about your Keytruda success. As a direct result of your post and this thread, my Stage IV MSS mom had an incredibly encouraging appointment this past week with Dr. VanDeusen at OSU (we live in Cincinnati) and will begin Keytruda in the next week or two.

For those following along, here's her backstory - my mom was diagnosed in 2014, stage iv, liver mets. In that time, she's been through many, many rounds of FOLFOX, FOLFIRI, and Lonsurf, as well as a liver resection, HAI pump insertion, radiation, and APR surgery. She's also had treatment, second opinion consults, and/or clinical trial consults at MSK, Dana Farber, OSU, and Sarah Cannon in Nashville. Currently she has 6 small lung mets and a suspicious lymph node. Liver is clear. Since being on FOLFOX and Lonsurf this past year, she continued to have slow but clear growth of her lung mets. Her local oncologist was unsure what to do next, but she is only 62, in great health otherwise, and has tons of energy, so she is not giving up the fight. We began exploring clinical trials and recently pushed for Foundation One testing of one of her lung mets, which revealed that she has a tumor mutation burden of 19(!!) and some significant frontline mutations (KRAS and others). She participated in a clinical trial at Sarah Cannon (https://clinicaltrials.gov/ct2/show/NCT03013491). First scan was stable, second scan showed growth just larger than 20% for some of the lung mets. There is a question as to whether that growth was pseudo-progression because of the immunotherapy trial drug, but the sponsor removed her from the trial. At this point, we began exploring other trial options but also began looking for other avenues outside of a trial.

After reading Cynthia's original post in this thread and her updates, we pushed my mom to go back to Ohio State for a consult with Dr. VanDeusen. Because of the results of her Foundation One testing and and the success of other cases, Dr. VanDeusen agreed that trying Keytruda is a logical next step. We have to clear some insurance related hurdles, but infusions should start in the next week or two.

A few takeaways - PLEASE push your doctors to do full genomic (i.e., Foundation One, Caris, etc.) testing of your cancer. Every single stage iv patient should have this testing. Also, it is SO important to educate yourself as much as possible on this disease and treatment developments. This forum, the COLONTOWN facebook groups, and websites like OncLive are great resources. Finally, you must push your doctors and advocate on behalf of yourself or your loved one who is the patient. The squeaky wheel gets the grease. My mom's been squeaking the wheel since 2014 - there is hope for stage iv patients!

I hope that in a few months, I will come back with a post on my mom's Keytruda success. Until then, thank you again Cynthia!!

-KCT

TeamRosie wrote:Hi Cynthia,

Thank you SO MUCH for posting your story about your Keytruda success. As a direct result of your post and this thread, my Stage IV MSS mom had an incredibly encouraging appointment this past week with Dr. VanDeusen at OSU (we live in Cincinnati) and will begin Keytruda in the next week or two.

For those following along, here's her backstory - my mom was diagnosed in 2014, stage iv, liver mets. In that time, she's been through many, many rounds of FOLFOX, FOLFIRI, and Lonsurf, as well as a liver resection, HAI pump insertion, radiation, and APR surgery. She's also had treatment, second opinion consults, and/or clinical trial consults at MSK, Dana Farber, OSU, and Sarah Cannon in Nashville. Currently she has 6 small lung mets and a suspicious lymph node. Liver is clear. Since being on FOLFOX and Lonsurf this past year, she continued to have slow but clear growth of her lung mets. Her local oncologist was unsure what to do next, but she is only 62, in great health otherwise, and has tons of energy, so she is not giving up the fight. We began exploring clinical trials and recently pushed for Foundation One testing of one of her lung mets, which revealed that she has a tumor mutation burden of 19(!!) and some significant frontline mutations (KRAS and others). She participated in a clinical trial at Sarah Cannon (https://clinicaltrials.gov/ct2/show/NCT03013491). First scan was stable, second scan showed growth just larger than 20% for some of the lung mets. There is a question as to whether that growth was pseudo-progression because of the immunotherapy trial drug, but the sponsor removed her from the trial. At this point, we began exploring other trial options but also began looking for other avenues outside of a trial.

After reading Cynthia's original post in this thread and her updates, we pushed my mom to go back to Ohio State for a consult with Dr. VanDeusen. Because of the results of her Foundation One testing and and the success of other cases, Dr. VanDeusen agreed that trying Keytruda is a logical next step. We have to clear some insurance related hurdles, but infusions should start in the next week or two.

A few takeaways - PLEASE push your doctors to do full genomic (i.e., Foundation One, Caris, etc.) testing of your cancer. Every single stage iv patient should have this testing. Also, it is SO important to educate yourself as much as possible on this disease and treatment developments. This forum, the COLONTOWN facebook groups, and websites like OncLive are great resources. Finally, you must push your doctors and advocate on behalf of yourself or your loved one who is the patient. The squeaky wheel gets the grease. My mom's been squeaking the wheel since 2014 - there is hope for stage iv patients!

I hope that in a few months, I will come back with a post on my mom's Keytruda success. Until then, thank you again Cynthia!!

-KCT

TeamRosie, I’m sending Good Luck wishes for success!
Thank you for telling your story and for pushing for testing like Foundation One. That testing is something I wish my husband’s Onc will agree to next time we meet her. You say your mother is MSS, can I ask what mutations you knew about before doing this Foundation One? Was Kras for example, not known before?
All the best to you!

Thank you all for sharing your experience with Pembrolizumab and MSS colon cancer. There is another hypothetical bio marker for checkpoint inhibitor response even for people with a low TMB.

The idea for this biomarker came from the fact that renal cancer has a high response to checkpoint inhibitors yet interestingly the responders do not have a high TMB (unlike for other cancers that respond to checkpoint blockade - lung, melanoma MSI high). Several studies have hypothesized that this is due a loss of function variant in the PBRM1 gene. Only about 1% of colon cancers have this mutation. I’m not aware of anyone with MSS and the PBRM1 mutation trying pembrolizumab. Has anyone heard of any news regarding this?


Below are relevant articles:
http://ascopubs.org/doi/abs/10.1200/JCO ... uppl.12091

https://cdn2.hubspot.net/hubfs/174278/U ... SR_lmg.pdf

Hi - That’s a good point/question. We did know her MSS and KRAS status prior to the Foundation One testing. I think we also know her BRAF status, but I’ll have to double check. She had Guardant 360 testing and MSK’s IMPACT testing prior to the Foundation One. However, prior to Foundation One, we didn’t know her tumor mutation burden. I believe the Foundation One report also identified some frameshift mutations that are correlated to immunotherapy success, but my understanding on that point is limited and it’s something I need to research further to understand. The other point is that with years of treatment, the cancer can change and the precision and technology of testing has improved over time, so updated testing was important to us. Hope that helps!

KCT:
I am so happy to read that Dr. VanDeusen is working with your Mom and that she has a treatment plan. Obviously, no one can say what treatments will or wont work for any given person....but because the FDA and insurance companies basically made a determination that immunotherapies did NOT work for MSS Colon Cancer patients, I felt it was very very important and my duty to share what we stumbled upon just by being diligent and open to thinking outside the box.

It is antidotal information and stories like this that helped guide me to MSK and Dr. Kemeny (which gave me that last 8 years) and then this amazing new treatment. So I hope that your Mom and many other people can benefit from my story.

Please keep us updated on her progress!
Cynthia