Keytruda....Working for MSS....Mutation Burden is the Key

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Jack&KatiesMommy
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Location: Columbus, OH

Re: Keytruda....Working for MSS....Mutation Burden is the Key

Postby Jack&KatiesMommy » Thu Aug 30, 2018 8:11 am

Steph20021 wrote:Thanks Dionca, I don’t know why foundation one quoted me more- unless cost has gone up or she quoted me for a different test. Either way I can’t afford it. So my plan is that I will start with getting a test done through a trial at PMH. I’ll speak with my oncologist tomorrow about it.
Hoping I can get a current biopsy done of a tumour I have now rather than my 4.5 year old banked stuff. I’ve done a lot of chemo since then.

Dionca wrote:
Steph20021 wrote:I wonder, can Canadians get Foundation One testing? What exactly am I asking them for, (just for “mutation burden testing of my tumour”) and how much could I expect to pay, any ideas?


Steph - here is a recent article posted on Colorectal Cancer Canada, that makes reference to the Foundation's mutation burden testing. It says the test is $5,800.

"All Cancer Patients Should Have Access To Genomic Testing"
http://archive.colorectalcancercanada.c ... ting/,5275
The novelty of Foundation’s approach—like that of a few other companies leading the field of cancer diagnostics—is the scope of testing. These laboratories examine hundreds of genes by a method called next-generation sequencing (NGS). For a price of $5800, in two weeks’ time, Foundation reports on tumor mutation burden (TMB), microsatellite instability (MSI), and mutations in any of 324 genes that may indicate sensitivity—or resistance—to oncology drugs.


Steph & Dionca:
You can apply for Financial Assistance....Foundation One is very generous in its application of the criteria. I am a lawyer and we are financially very comfortable. But when I applied I listed my dependents and my medical bills, house mortgage, cars, etc. and my financial responsibility was reduced by 60%. I would suggest that you call Foundation One and ask about this potion.
Cynthia
Cynthia
Mommy to Jack (8) now (18) and Katie (4) now (14)
(My Most Precious Things)
Dx 8/11 Stage IV CRC (liver mets) CEA 2,600+
9/11 Folfiri 2/12: Failed Liver Resection
5/12 HAI pump/removed primary
4/13 Liver Resection
8/13-12/15 (10) RFAs lungs
5/17: Upper Left Lobe of lung resected.
02/18: 3 new lymph mets lung
05/18: Keytruda (MSS w/Intermediate TMB): NED CEA: 66.4, 39.2, 23.8, 13, 3.5 1.8, 1.0, 2.8 3.9, 5.0, 5.6, 1.5, .8,

boswind
Posts: 74
Joined: Fri Apr 11, 2014 12:04 pm

Re: Keytruda....Working for MSS....Mutation Burden is the Key

Postby boswind » Mon Sep 10, 2018 1:50 pm

When I was seen by my oncologist last week, I mentioned to him the tumor mutation burden and possibility of MSS patient responding to Keytruda. He said he would put me on a study program immediately and I would be tested extensively regarding gene mutation. If I have "right" mutations, I will be given Keytruda right away. Furthermore, the study program will pay for the cost of all gene mutation testing.
01.24.14 Male, DX @54 Rectosigmoid Cancer, MRI: T3N0M0
03.19.14 Completed 5-week Radia+Xeloda
05.07.14 Had surgery
02.25.15 CT showed stage 4 inoperable
03.15 - 08.15, folfox + Avastin
08.15 - 07.17, 5FU+leucovorin+Avastin
07.17 - 01.18, Folfuri + Avastin
02.18 - 03.19, Centuximab + Irinotecan
03.19 - 05.19, Keytruda
05.19 - 9.19, Folfox+Avastin
10.19 -01.20: Centuximab+Irinotecan
03.20 - 06.20: STIVARGA
07.20 - present: lonsurf+Avanstin
MSS, KRAS wt, BRAF wt
131 rounds of chemos received (as of 12.31.20)

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Jack&KatiesMommy
Posts: 640
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Location: Columbus, OH

Re: Keytruda....Working for MSS....Mutation Burden is the Key

Postby Jack&KatiesMommy » Tue Sep 11, 2018 10:08 am

boswind wrote:When I was seen by my oncologist last week, I mentioned to him the tumor mutation burden and possibility of MSS patient responding to Keytruda. He said he would put me on a study program immediately and I would be tested extensively regarding gene mutation. If I have "right" mutations, I will be given Keytruda right away. Furthermore, the study program will pay for the cost of all gene mutation testing.


That is great! Where are you seen? This I great news for anyone in your area that is MSS. I'll keep my fingers crossed that you have a solid mutation burden. Please come back and let us know.
Cynthia
Cynthia
Mommy to Jack (8) now (18) and Katie (4) now (14)
(My Most Precious Things)
Dx 8/11 Stage IV CRC (liver mets) CEA 2,600+
9/11 Folfiri 2/12: Failed Liver Resection
5/12 HAI pump/removed primary
4/13 Liver Resection
8/13-12/15 (10) RFAs lungs
5/17: Upper Left Lobe of lung resected.
02/18: 3 new lymph mets lung
05/18: Keytruda (MSS w/Intermediate TMB): NED CEA: 66.4, 39.2, 23.8, 13, 3.5 1.8, 1.0, 2.8 3.9, 5.0, 5.6, 1.5, .8,

mhf1986
Posts: 158
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Location: near DC

Re: Keytruda....Working for MSS....Mutation Burden is the Key

Postby mhf1986 » Fri Oct 05, 2018 11:21 am

:?: :?:

Can anyone tell me where a study program in the US is or give me reference to a scholarly article about this? DH liver tumors, lymph nodes, and lung things grew again after only 5 months on Vectibex/Irinotican. The July scan showed shrinkage of a liver tumor to 3cm and now it's bounced up to 7cm, as large as its been since starting at 10cm 2 years ago at diagnosis.

I mentioned the Foundation One testing for tumor mutation to try Keytruda and Dr. told me they had all the info they needed abut DH and no MSS patient was showing benefit from Keytruda. This is the same response I've gotten when I asked about immunotherapy and NIH "Sleen" trial. So I'm going out on my own to find something because I just don't think this guy is willing to be creative.

Here we sit, between DC and Baltimore and I'm getting these kinds of answers??

Thanks,
m
Caregiver to DH, dx @ 50, mets to liver/lungs, MSS, wild
9/16 CEA 114, blockage, left hemi, perm. colostomy
11/16 port in, FOLFOX + Avastin
6/17 CEA 15, 5FU + A only due to neuropathy
11/17 CEA 38, CAPOX + A
1/18 CAPOX = hi bilirubin/bad hfs, back to FOLFOX + A
5/18 growth; Vectibex + 75% Irinotecan
7/18 CEA 23, shrinkage
10/18 CEA 28, growth of 2 liver tumors/shrinkage of few and lung nodes
11/18 Lonsurf, looking at spheres, proton, trials
11/19/18 Peace

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Jack&KatiesMommy
Posts: 640
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Location: Columbus, OH

Re: Keytruda....Working for MSS....Mutation Burden is the Key

Postby Jack&KatiesMommy » Fri Oct 05, 2018 2:22 pm

Call Foundation One. They are the ones amassing all of the data on this. They are the ones who alerted my oncologist in Ohio to this. You can ask your oncologist to call mine as I am certain he will talk to him about the success he has had with Keytruda and MSS at the Ohio State University Cancer Center. His name is Dr. Jeffrey Vandeusen.
Last edited by Jack&KatiesMommy on Sat Oct 20, 2018 11:33 pm, edited 1 time in total.
Cynthia
Mommy to Jack (8) now (18) and Katie (4) now (14)
(My Most Precious Things)
Dx 8/11 Stage IV CRC (liver mets) CEA 2,600+
9/11 Folfiri 2/12: Failed Liver Resection
5/12 HAI pump/removed primary
4/13 Liver Resection
8/13-12/15 (10) RFAs lungs
5/17: Upper Left Lobe of lung resected.
02/18: 3 new lymph mets lung
05/18: Keytruda (MSS w/Intermediate TMB): NED CEA: 66.4, 39.2, 23.8, 13, 3.5 1.8, 1.0, 2.8 3.9, 5.0, 5.6, 1.5, .8,

mhf1986
Posts: 158
Joined: Sat Mar 11, 2017 8:30 pm
Location: near DC

Re: Keytruda....Working for MSS....Mutation Burden is the Key

Postby mhf1986 » Fri Oct 05, 2018 7:00 pm

Thank you so much! A good place to start.

DH surprised everyone with FOLFOX working for 18 months. Now he's surprising everyone with the Vectibex+Irinotican only working 4 months. It was such a big surprise because the CEA was mostly stable and the liver function tests were looking good. No one expected the CT scan to show such growth so soon. Dr. thought it would be another 8 months to a year before we had to have this conversation about next drug and clinical trials. But every time I bring something untried up, it's Nope, not gonna help. Dr. is going to look into clinical trials and call us next week but I'm going to do my own research.
Caregiver to DH, dx @ 50, mets to liver/lungs, MSS, wild
9/16 CEA 114, blockage, left hemi, perm. colostomy
11/16 port in, FOLFOX + Avastin
6/17 CEA 15, 5FU + A only due to neuropathy
11/17 CEA 38, CAPOX + A
1/18 CAPOX = hi bilirubin/bad hfs, back to FOLFOX + A
5/18 growth; Vectibex + 75% Irinotecan
7/18 CEA 23, shrinkage
10/18 CEA 28, growth of 2 liver tumors/shrinkage of few and lung nodes
11/18 Lonsurf, looking at spheres, proton, trials
11/19/18 Peace

RulaLenska
Posts: 24
Joined: Fri May 04, 2018 8:13 pm

Re: Keytruda....Working for MSS....Mutation Burden is the Key

Postby RulaLenska » Fri Oct 19, 2018 10:45 pm

Jack&KatiesMommy wrote:i wanted to give you all an update on my off-label use of Keytruda (since I am MSS it is not approved for use by me....since it doesn’t generally work for colon cancer patients which microsatellite stable tumors.)

HOWEVER, it looks like it is working for me....and here is the reason why (according to my doctor and the Foundation One reps): it is not whether the tumor is ZmSS or MSI that is determinative as to whether the immunotherapy will work....it is the THE TUMOR’S MUTATION BURDEN THAT DETERMINES WHETHER KEYTRUDA WILL WORK.

Foundation One is seeing evidence that people whose tumors have a high (or moderately high) mutation burden tend to respond to the immunotherapy treatments. Generally MSI tumors have a high mutation burden and MSS tumors have just one or two mutations if any. In my case (probably dilute to the fact that I’ve had many different courses of treatments over the kart 7 years) my ZmSS tumor has a moderate mutation burden (11 mutations.). So my local oncologist (who has been doing tons of work with immunotherapy over the last 6 years) got permission to treat me with Keytruda off-label.

My CEA (which is super sensitive and very accurate over the last 7 years) was 39.6 before my first Keytruda treatment. Three weeks later, before my second treatment, my CEA had risen to 66.4. Before my third treatment, my CEA was back down to 39.2, and three weeks later before my 4th treatment it was down to 13.0. On Friday, before my 5th treatment my CEA was down to 3.5 and my CT scan showed shrinkage of the only slightly enlarged lymph nodes in my hilar lung area to normal size.

This is an amazing breakthrough for MSS patients. If you are MSS, please get Foundation One Testing to see if you have a moderate or high mutation burden. If you do, immunotherapy couldvwork for you.

Please feel free to contact me if you have questions.
Cynthia

I too am MSS but with a low mutation burden. I have a variant on a PolE gene that has intrigued my oncologist since diagnosis and initial testing. The timing of my treatments has been very fortunate and that appears to continue. I’m healing from my liver resection and my latest CT shows 3 tiny tumors on my regrowth. Since I responded exquisitely to my previous chemo regimes (switched only due to side effects) we still have some of those in the tool kit. While these are still tiny we want to try Ketruda so my oncologist has applied for this. May need to appeal directly to pharmaceutical company as it will be off label. Onc says I could “ride this pony” for years if I respond. With minimal side effects. I will be treated with something in about a month. It may be Ketruda or Irinitecan/Vectibix . Two years ago I was very sick, not a candidate for surgery and very scared. Today I feel alive and hopeful and fortunate to be here. That being said...neuropathy REALLY sucks!
Cyn
Dx 8/16 IV stage with mets to lungs liver adrenals
KRAS wt MSS CEA over 400
2 x folfori caused refractory diarrhea but dropped CEA to 200
Switched to folfox stopped after 10 due to neuropathy
Avastin leucorvorin 5fu dropped after 11 due to hfs
Chemo break to travel.
Nov. 2017 emergency sleeve colectomy of primary tumor.
Vectibix irinotecan
PET scan shows no lung or adrenal tumors
5/2 Portal Vein Embolisation in preparation for liver resection.
6/12 extended right resection removing 60%.

RulaLenska
Posts: 24
Joined: Fri May 04, 2018 8:13 pm

Re: Keytruda....Working for MSS....Mutation Burden is the Key

Postby RulaLenska » Wed Nov 14, 2018 9:51 pm

I just found out after an appeal that I will be receiving Keytruda. I’ll be getting schedule details in the next day or two. I’m pretty excited/nervous about this. I haven’t had any treatment since May when I started preparing for liver resection.
Cynthia (my name also!) I am interested in your experience so far. Any side affects worth noting? Any infusion day issues? Thanks for sharing your info.
Cyn
Dx 8/16 IV stage with mets to lungs liver adrenals
KRAS wt MSS CEA over 400
2 x folfori caused refractory diarrhea but dropped CEA to 200
Switched to folfox stopped after 10 due to neuropathy
Avastin leucorvorin 5fu dropped after 11 due to hfs
Chemo break to travel.
Nov. 2017 emergency sleeve colectomy of primary tumor.
Vectibix irinotecan
PET scan shows no lung or adrenal tumors
5/2 Portal Vein Embolisation in preparation for liver resection.
6/12 extended right resection removing 60%.

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Jack&KatiesMommy
Posts: 640
Joined: Wed Dec 21, 2011 1:08 pm
Location: Columbus, OH

Re: Keytruda....Working for MSS....Mutation Burden is the Key

Postby Jack&KatiesMommy » Fri Nov 16, 2018 11:57 am

Hi Cyn:
SOOOO happy for you and I will pray that it works for you as wella s it has for so many others! I have found Keytruda to be a breeze! (after having gone through Folfox, Irinotecean, Avastin, Xeloda)...Keytruda is wonderful. It is only a 30 minute infusion. The one and only side effect that I have experienced is fatigue...and it is pretty bad...but I still work 45-50 hours a week as a lawyer, take my kids to and from swimming, dance, school events, etc. and manage to run a small animal rescue on the side. So even the fatigue is tolerable. I know that there can be other side effects (shortness of breath--which I have but more from all of the rfa's that I have had and the resection of a lobe of my right lung) and skin issues, but those are all that I have heard mentioned...and I had none of them, with the exception of fatigue. Good luck and please let us know how it goes!
Cynthia
Cynthia
Mommy to Jack (8) now (18) and Katie (4) now (14)
(My Most Precious Things)
Dx 8/11 Stage IV CRC (liver mets) CEA 2,600+
9/11 Folfiri 2/12: Failed Liver Resection
5/12 HAI pump/removed primary
4/13 Liver Resection
8/13-12/15 (10) RFAs lungs
5/17: Upper Left Lobe of lung resected.
02/18: 3 new lymph mets lung
05/18: Keytruda (MSS w/Intermediate TMB): NED CEA: 66.4, 39.2, 23.8, 13, 3.5 1.8, 1.0, 2.8 3.9, 5.0, 5.6, 1.5, .8,

RulaLenska
Posts: 24
Joined: Fri May 04, 2018 8:13 pm

Re: Keytruda....Working for MSS....Mutation Burden is the Key

Postby RulaLenska » Fri Nov 16, 2018 8:38 pm

Thank you Cynthia for the feedback. I’ve heard from two others on Keytruda who also say that fatigue is their only side affect. You sound like a real dynamo so I wonder if any treatment would slow you down!
Best wishes,
Cyn
Dx 8/16 IV stage with mets to lungs liver adrenals
KRAS wt MSS CEA over 400
2 x folfori caused refractory diarrhea but dropped CEA to 200
Switched to folfox stopped after 10 due to neuropathy
Avastin leucorvorin 5fu dropped after 11 due to hfs
Chemo break to travel.
Nov. 2017 emergency sleeve colectomy of primary tumor.
Vectibix irinotecan
PET scan shows no lung or adrenal tumors
5/2 Portal Vein Embolisation in preparation for liver resection.
6/12 extended right resection removing 60%.

Spazzyjanet
Posts: 54
Joined: Mon Oct 01, 2018 3:28 pm
Facebook Username: Heather Stoker

Re: Keytruda....Working for MSS....Mutation Burden is the Key

Postby Spazzyjanet » Sat Nov 17, 2018 9:16 am

I've had Genomic testing. I am MSS. KRAS G12V. I have ERG and VEGF Amplifications. I have no idea what a "high tumor burden" is. How do I tell if this is good news for me or bad news?
40 yr old, 3 kids. Dx 9/2018, Stage IV
KRAS G12V (resistant to Cetuximab)
CEA levels normal at diagnosis
4.2 cm Tumor, PT3, PN2B
11 of 18 with adenocarcinoma
+ removal of one cancerous node in Peritoneum.
9/2018, Colon resection and Ostomy-- Margins Negative
10/2018, PET shows 6 liver mets
10/2108, begin FOLFOX (Oxi+5 FU)
11/2018, MRI updates potential liver metastasis to 11 mets, both lobes.

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Sophy
Posts: 261
Joined: Fri May 27, 2011 2:46 am
Location: New Zealand

Re: Keytruda....Working for MSS....Mutation Burden is the Key

Postby Sophy » Sat Nov 17, 2018 7:37 pm

So pleased to hear this is working for you, wonderful news. Well done and thank you for sharing the information about it. :D
dx T3N1M0 Feb 2011 when children age 11, 7 and 2
Xeloda/rad March 11, LAR June 11 temp ileo
Xelox 6 rounds, NED
Lung mets Oct 13
Laser surgery Germany Jan 14. 3 mets left lung.
Laser surgery UK Jun and Aug 14 one met each lung, NED
Aug 14 Started Xeloda and Celebrex (ADAPT)
June 20 CT shows nodule, bronchoscopy confirms is scar tissue, still NED
Dec 20 stopping Xeloda continue celebrex, cimetedine
Aug 21,March 23 scans show still NED
March 2023 CURED - discharged from Oncology, no more scans or follow up

chadwick1
Posts: 28
Joined: Sat Oct 13, 2018 9:04 am
Location: Upstate NY

Re: Keytruda....Working for MSS....Mutation Burden is the Key

Postby chadwick1 » Wed Dec 19, 2018 10:29 pm

I just got the results of my genomic testing back and I’m really interested in this thread because it seems like I might fall into the same boat. I’m confirmed MSS, but it states the estimated tumor mutation burden to be 13.2 mutations per megabase. Incidentally, this was also an MSK-IMPACT report—crazylife did your report not state a tumor mutation burden? I wonder if they just started doing that. Searching around I have seen a lot of articles just in recent months about this effect (some links below), so maybe it’s gaining mindshare and they’ve added it.

Cynthia (also my mom’s name!), I’m curious if that is the key thing you got from the Foundation One test or if I should be looking at that for any other information. You mentioned getting permission to use Keytruda off-label, was there anything special you (or your onc) had to do to facilitate that?

I’ve read that being MSS but having a high TMB is uncommon (only 3% of cases according to link #2), so maybe this could be a lucky break, relatively speaking!

1: Evidence Builds for Tumor Mutational Burden as Immunotherapy Biomarker (9/2018)
2: Beyond microsatellite testing: assessment of tumor mutational burden identifies subsets of colorectal cancer who may respond to immune checkpoint inhibition (8/2018)
3: Significance and implications of FDA approval of pembrolizumab for biomarker-defined disease (5/2018)
DX 2017, 37yo father of two
Stage 3b RC (T3N1bM0) normal CEA, KRAS G12V
Radiation + 5FU
LAR w/ temp loop ileo. 2/33 lymph
FOLFOX, 9 rounds
2018 CT mass in liver & lung
MRI confirms liver, Stage 4
Liver resection
2019 lung nodule shrank, monitor
Lung nodule grew again, resection
2020 CT new lung nodule + 2 lymph nodes
FOLFIRI, good response
2021 pause FOLFIRI, attempt lobectomy, aborted
Radiation to lung

Wonderfullymade
Posts: 140
Joined: Tue Jan 12, 2016 4:33 pm

Re: Keytruda....Working for MSS....Mutation Burden is the Key

Postby Wonderfullymade » Thu Dec 20, 2018 9:09 am

This is fascinating and fantastic news! A few more of us are able to get a treatment that works!
Thank you for the links!
I also got Keytruda off label because it was not approved at the time I needed it. My Dr appealed to my ins co on the grounds of it being a lifesaver for me. At the time there was one study...a small study that showed dramatic results in msi-h patients.
I think the links you have provided are good and should be able to help in your application if your Dr doesn’t have enough amo!

Man! Good luck!
Wonderfullymade
DX 3/2015 53
Stage IVa CC w/liver met
BRAF/KRAS wild type MSI-High (MLH1, PMS2) not Lynch
Folfox 3 cycles
5/2015 ER for subtotal colectomomy due to perforated colon, ovary removed
Folfuri/Pantiumumab 5 cycles
8/2015 liver resection, gallbladder removed and new LN
10/2015 CT scan new nodes
10/2015 Pembro started CEA 2.2
5/2017 stable lung things, coltis, lymph nodes stable cea 1/2017 1.1
9/2017 NED CEA 1.1 ( stopped Pembro)
2/2019 ER for DVT/ PE
2/2019 clean CT (NED) CEA 1.1

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Jack&KatiesMommy
Posts: 640
Joined: Wed Dec 21, 2011 1:08 pm
Location: Columbus, OH

Re: Keytruda....Working for MSS....Mutation Burden is the Key

Postby Jack&KatiesMommy » Thu Dec 20, 2018 9:19 am

chadwick1
My oncology team prepared an appeal to my insurance company and to Keytruda's manufacturer explaining the new evidence that there may be benefit to MSS colon cancer patients that have a high mutation burden. They worked with Foundation One (who had amassed a lot of data based on their testing and that helped. Bothe the drug company and my insurance company agreed to cover the drug's use in my case based on the appeal and the evidence submitted by my oncology team.
Cynthia
Mommy to Jack (8) now (18) and Katie (4) now (14)
(My Most Precious Things)
Dx 8/11 Stage IV CRC (liver mets) CEA 2,600+
9/11 Folfiri 2/12: Failed Liver Resection
5/12 HAI pump/removed primary
4/13 Liver Resection
8/13-12/15 (10) RFAs lungs
5/17: Upper Left Lobe of lung resected.
02/18: 3 new lymph mets lung
05/18: Keytruda (MSS w/Intermediate TMB): NED CEA: 66.4, 39.2, 23.8, 13, 3.5 1.8, 1.0, 2.8 3.9, 5.0, 5.6, 1.5, .8,


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