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

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Lydia666
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Re: Keytruda....Working for MSS....Mutation Burden is the Key

Postby Lydia666 » Thu Dec 20, 2018 10:08 am

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

Thank you, this is valuable information. We'll see.
Oct 2012- thyroid cancer
June 19, 2015 Dx@39 yrs- CRC-T3N1M0
No vascular, no perineural invasion
Aug-Sept 2015- 28 rad/5FU
Oct 28, 2015- LAR- temp ileo, neg. nodes- 0/11
March 2016- 6 rounds Xeloda/positive CHEK2 mutation
August 2016- DCIS and decided post prophylactic double mastectomy
May 2018 - clean CT
Sept 2018-clean scope
Devastation, total shock- oct 2018, invasion of peri mets
Dec 20 - 2 round of folfox
Mom to 4 & 7 yrs kids - at least i brought them to this level of independence.

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

Postby Jack&KatiesMommy » Thu Dec 20, 2018 1:27 pm

Here is a link to a Foundation One Article that is , in part, based upon the results of my case and relates specifically to MSS TMB and Colorectal Cancer's response to immunotherapy:

https://www.foundationmedicine.com/blog ... tal-cancer
Cynthia
Mommy to Jack (8) now (16) and Katie (4) now (12)
(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 mets lymph nodes lung:
05/18: Keytruda (MSS w/Intermediate TMB): 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, .8, 1.1, 1.1, .7
7/18; 9/18; 11/18; 2/19 Clear CT scans

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

Postby juliej » Thu Dec 20, 2018 4:18 pm

Jack&KatiesMommy wrote:Here is a link to a Foundation One Article that is , in part, based upon the results of my case and relates specifically to MSS TMB and Colorectal Cancer's response to immunotherapy:

https://www.foundationmedicine.com/blog ... tal-cancer

Thanks for providing this information for everyone and keeping it at the top of the forum!

It's so cool they looked at tumor mutational burden (TMB) and not just MSS status! This opens the door to checkpoint inhibitor therapy for thousands more patients who would have been locked out. And you are a pioneer of this approach! :D :D :D

Go, Cynthia, go! You're doing awesome!

xo,
Juliej
Stage IV, liver/lung mets 8/4/2010
Xelox+Avastin 8/18/10 to 10/21/11
LAR, liver resec, HAI pump 11/11
Double lung surgery + ileo reversal 2/12
Adjuvant Xeloda 3-9/12
VATS rt. lung 12/21/12 - benign granuloma!
NED 3/17/12 to 2/1/2019, CEA<1

chadwick1
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Re: Keytruda....Working for MSS....Mutation Burden is the Key

Postby chadwick1 » Thu Dec 20, 2018 8:49 pm

Thanks all for the replies and thank you Cynthia for bringing this to our attention! Sounds like if we need more evidence I could get in touch with Foundation One and possibly take their test too, but I’ll talk to my onc and see what she thinks and if there’s a good case already. I need to wait till next month to get another scan before doing anything anyway, but it’s exciting that this could potentially be a really effective treatment!
DX 6/2017, 37yo father of two
Stage IIIb rectal cancer (T3N1bM0) no genetic indicators, normal CEA
7/2017 radiation + 5FU
10/2017 LAR w/ temp loop ileo. clear margins, 2/33 nodes
11/2017-3/2018 FOLFOX, 9 rounds
2/2018 clear CT
4/2018 ileo reversal
10/2018 CT shows suspicious mass in liver (1.7 cm), and in lung (0.6 cm)
MRI confirms 1 liver met, Stage IV
11/2018 liver resection, clear margins
1/2019 CT: lung node shrank to 0.3 cm
3/2019 CT: unchanged/clear!

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

Postby lpas » Fri Dec 21, 2018 3:26 pm

This is just an FYI for anyone who has an older report from Foundation One. I had the Foundation One test done a few months after my initial diagnosis in January 2015. Decided to pull it out and check for TMB after seeing this thread, but couldn't find the information, so I thought I'd call them. My report says right on the front page that I have eight "genomic alterations" with an additional 16 of unknown significance listed in an Appendix, but apparently, genomic alternations (like KRAS, TP53, etc.) aren't equivalent to mutational burden. The customer service rep advised that they weren't testing for mutational burden back in 2015 but would be happy to go back and do so now if they could still pull the information from my sample--no extra charge. He also said they would update the research section (possible clinical trials, etc.) on my genomic alterations, since quite a bit has changed since 2015.

So if anyone is like me and has an old Foundation One report you should definitely call them to have it updated! Very, very impressed with their customer service. I feel very fortunate not to "need" this info at the moment but knowing (from a recent RGCC test) that I still have circulating tumor cells, I like to be prepared. And thanks so much to Cynthia for posting this information!!
11/14 Dx sigmoid CC @ 45yo
12/14 Colectomy + hysterectomy
Stage IIIB, T3N1bM0, 2/20 nodes, MSS, G2, KRAS(A146T), TP53, SMAD4, ERBB2, CEA 1.0
2/15-7/15 XELOX & Celebrex
4/18 clean CT
2/19 clean scope
Ongoing Celebrex, Tagamet & other carefully-targeted supplements
Post-chemo CEA 3.0, 2.5, 2.3, 2.0, 1.6, 1.3, 1.8, 2.1, 1.8, 2.0, 1.8, 1.9, 1.7, 1.5, 1.6, 1.5, 1.4, 1.4, 1.3, 1.3, 1.6, 1.6, 1.3, 1.4, 1.6, 2.2, 2.4, 2.1 and ? For sanity's sake I've stopped looking.
Mom to a 5 & 7yo

strongmama
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Joined: Wed Jan 02, 2019 12:28 am

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

Postby strongmama » Wed Jan 02, 2019 9:11 pm

Are there any other MSS people here with intermediate TMB having good results on Keytruda or Opdivo?

Cynthia how long have you been on Keytruda?
I've heard that being intermediate and either on Keto or having low blood surgar may help.
Would you say that could be a factor for you?

One person I know of who has had response and has a TMB of 13 thinks it could be having had Y90.
Have you had Y90?

I'm just trying to figure out who with intermediate TMB may or may not be a responder.
Thanks for any information!

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

Postby Jack&KatiesMommy » Fri Jan 04, 2019 8:26 pm

Strong Mama...since Keytruda and Optivo have not been approved for use in colon cancer with MSS characteristics, you probably won't find many people with MSS that have been fortunate enough to have had the opportunity to be treated with it. Their doctors would need to request use of the drug "off label." The studies are starting to suggest that tumor burden may be more predictive of response to the immunotherapy treatments so doctors are starting to make this request. But as of now....there have not ben a lot of MSS Colon Cancer patients that have been treated with it.

I have been on Keytrud since May 2018 (8 months now). I have been NED with a CEA int he normal range (and my CEA is extremely predictive of cancer for me historically) for the last 6 months. I do not do Keyto or have low blood sugar at least not that I am aware. I pray a lot and believe with my heart that God has played a major role in my survival.

Cynthia
Cynthia
Mommy to Jack (8) now (16) and Katie (4) now (12)
(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 mets lymph nodes lung:
05/18: Keytruda (MSS w/Intermediate TMB): 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, .8, 1.1, 1.1, .7
7/18; 9/18; 11/18; 2/19 Clear CT scans

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

Postby strongmama » Sun Jan 06, 2019 2:43 am

Hi Cynthia!
Thank you for your reply!! I believe TMB is a factor as well. I have read of MSS patients with high TMB having response and there seems to be research supporting this, but I have not come across as much about intermediate TMB. My daughter is stage 4 and has a TMB of 12 so we are planning to ask her oncologist about the possibility of adding Keytruda to her Folfox. There are some MSS trials combining chemo with PD-L1 and research indicating it may help enhance the effectivity of immunotherapy.

I think with intermediate TMB responsiveness may be more questionable than high TMB, but we won't know unless we try. I do hope and pray my daughter has a similar response. Thank you for bringing hope. I do believe we will see some very good therapies and more treatment breakthroughs very soon.

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

Postby Jack&KatiesMommy » Mon Jan 07, 2019 4:24 pm

StrongMama: FWIW, my TMB is 12.
Last edited by Jack&KatiesMommy on Fri Jan 11, 2019 12:58 pm, edited 1 time in total.
Cynthia
Mommy to Jack (8) now (16) and Katie (4) now (12)
(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 mets lymph nodes lung:
05/18: Keytruda (MSS w/Intermediate TMB): 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, .8, 1.1, 1.1, .7
7/18; 9/18; 11/18; 2/19 Clear CT scans

mpbser
Posts: 854
Joined: Wed Apr 19, 2017 11:52 am

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

Postby mpbser » Tue Jan 08, 2019 8:20 am

I love this thread. I come back to it from time to time because I think that immunotherapy could be a great option for my husband who has a TMB of around 11 or so as well. Jackandkatiesmommy, do you go to the Cleveland Clinic? My husband is at a crossroads between Mass General and MSK. I don't know if either would entertain the idea of Keytruda off-label for him.
Wife 4/17 Dx age 45
5/17 - Lap left
Adenocarcinoma
5 x 4 x 1 cm
low grade
T3 N2b M1a
Stage IV A
8/17 Sub-total colectomy
2nd tumor 5.5 cm T1 N0
lymph nodes: 9 of 96
CEA: 2.9 to 2.2
MSS/MSI-L
Lynch no; KRAS wild
Immunohistochemsistry Normal
Tumor DNA variants: MTOR, APC, TP53
1/18 Liver left hepatectomy seg 4
5/18 CT clear
12/18 MRI shows 1 met in liver
Resection & HAI Mar 7
Folfiri & FUDR started Apr 1

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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 » Tue Jan 08, 2019 11:54 am

mpbster
I go to MSK & The James Cancer Center in Columbus.
Cynthia
Mommy to Jack (8) now (16) and Katie (4) now (12)
(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 mets lymph nodes lung:
05/18: Keytruda (MSS w/Intermediate TMB): 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, .8, 1.1, 1.1, .7
7/18; 9/18; 11/18; 2/19 Clear CT scans

strongmama
Posts: 3
Joined: Wed Jan 02, 2019 12:28 am

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

Postby strongmama » Tue Jan 08, 2019 4:18 pm

Cynthia it looks like you've had radiation? The person I mentioned with 13 TMB said there were a couple of other responders on her trial. Besides being MSS with intermediate TMB they all had Y-90.... so they suspect something with radiation may have helped. What are your thoughts on this? Have you heard anything like that from your oncologists?

Again, thank you for sharing your experience!

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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 » Tue Jan 08, 2019 10:18 pm

No radiation here. That would have always been a very last resort for me....particularly in the lung area. I had multiple radio frequency ablations though.
Cynthia
Mommy to Jack (8) now (16) and Katie (4) now (12)
(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 mets lymph nodes lung:
05/18: Keytruda (MSS w/Intermediate TMB): 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, .8, 1.1, 1.1, .7
7/18; 9/18; 11/18; 2/19 Clear CT scans

bdoyle
Posts: 3
Joined: Sun Dec 09, 2018 9:50 pm

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

Postby bdoyle » Thu Jan 10, 2019 2:04 pm

Cynthia,

Did you do any diet changes while on keytruda or take any additional suppliments?

Thank you,

Brian

bdoyle
Posts: 3
Joined: Sun Dec 09, 2018 9:50 pm

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

Postby bdoyle » Thu Jan 10, 2019 3:28 pm

Cynthia,

Also, is there any chance you might be able to share your mutations according to the Foundation One Report? I will be more than happy to share mine as well.

Thank you,

Brian


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