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

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Jack&KatiesMommy
Posts: 560
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 Jan 11, 2019 12:58 pm

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
Mommy to Jack (8) now (15) 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
7/18; 9/19; 11/18 Clear CT scans

Ljj1
Posts: 1
Joined: Mon Jan 14, 2019 8:16 pm

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

Postby Ljj1 » Mon Jan 14, 2019 8:58 pm

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!

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Jack&KatiesMommy
Posts: 560
Joined: Wed Dec 21, 2011 1:08 pm
Location: Columbus, OH

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

Postby Jack&KatiesMommy » Tue Jan 15, 2019 10:15 am

Cynthia
Mommy to Jack (8) now (15) 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
7/18; 9/19; 11/18 Clear CT scans

Pyro
Posts: 57
Joined: Mon Oct 12, 2015 7:40 pm
Location: Tucson, AZ

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

Postby Pyro » Tue Jan 15, 2019 2:07 pm

Keytruda side effects? At least the ones you saw?
Aug 2015- Diag Stage 4 CC with mets to liver (38/m)
Sep 2015- Avastin/Folfox/Iron
Dec 2015-Not a surgery candidate for liver
Jan 2016- Erbitux/Folfiri, 2nd opinion at MDA in TX
Feb 2016 -MD Anderson liver surgery, Dr. Vauthey
Mar 2016 -30% of left lobe removed, PVE
May 2016 - 70% of liver removed
Jun 2016-Radiation
Jan 2017-permanent colost @ MDA
Jul 2017-Erb/FOLFURI
Nov 2017 -Lung & Liver ablations@MDA
Jan 2018 -Xeloda & Avastin mx
Jul 2018-Avast/FOLFURI
Sep 2018-Radiation
Chemo for life

User avatar
Jack&KatiesMommy
Posts: 560
Joined: Wed Dec 21, 2011 1:08 pm
Location: Columbus, OH

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

Postby Jack&KatiesMommy » Wed Jan 30, 2019 10:49 pm

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.
Cynthia
Mommy to Jack (8) now (15) 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
7/18; 9/19; 11/18 Clear CT scans

mpbser
Posts: 684
Joined: Wed Apr 19, 2017 11:52 am

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

Postby mpbser » Thu Jan 31, 2019 7:31 am

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.
Wife 4/17 Dx age 45
5/17 - Lap left hemi
Adenocarcinoma
5 x 4 x 1 cm
low grade
T3 N2b M1a
Stage IV A
lymph nodes: 9 of 54
8/17 Sub-total colectomy
2nd tumor 5.5 cm T1 N0
CEA: 1.4, 2.1, 1.5, 1.9, 1.9, 2.1, 2.1, 2.4, 1.7, 2.0, 2.9, 2.2
MSS/MSI-L
Lynch no; KRAS wild
Immunohistochemsistry: Normal MLH1, MSH2, MSH6, and PMS2
Tumor DNA variants: MTOR, APC, TP53
1/18 Liver left hepatectomy seg 4
5/18 CT clear
12/18 MRI shows met
Resection & HAI Mar 7??

User avatar
Jack&KatiesMommy
Posts: 560
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 Jan 31, 2019 3:17 pm

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.
Cynthia
Mommy to Jack (8) now (15) 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
7/18; 9/19; 11/18 Clear CT scans

User avatar
GrouseMan
Posts: 790
Joined: Mon Aug 12, 2013 12:30 pm
Location: SE Michigan USA

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

Postby GrouseMan » Fri Feb 01, 2019 8:53 am

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
DW 53 dx Jun 2013
CT mets Liver Spleen lung. IVb CEA~110
Jul 2013 Sig Resct
8/13 FolFox,Avastin 12Tx mild sfx, Ongoing 5-FU Avastin every 3 wks.
CEA: good marker
7/7/14 CT Can't see the spleen Mets.
8/16/15 CEA Up, CT new abdominal mets. Iri, 5-FU, Avastin every 2 wks.
1/16 Iri, Erbitux and likely Avastin (Trial) CEA going >.
1/17 CEA up again dropped from Trial, Mets growth 4-6 mm in abdomen
5/2/17 Failed second trial, Hospitalized 15 days 5/11. Home Hospice 5/26, at peace 6/4/2017

boswind
Posts: 46
Joined: Fri Apr 11, 2014 12:04 pm

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

Postby boswind » Thu Feb 07, 2019 5:15 pm

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.
01.24.2014 Male, DX @54 Rectosigmoid Cancer, MRI: T3N0M0
03.19.2014 Completed 5-week Radia+Xeloda
05.07.2014 Had surgery
02.25.2015 CT showed liver and L4 Spine involvement.
03.2015 - 08.2015, folfox + Avastin
08.2015 - 07.2017, 5FU + leucovorin + Avastin for Maintenance
07.2017 - 01.2018, Folfuri + Avastin
01.25.2018 - present, Centuximab + Irinotecan
90 rounds of chemos received (as of 12.27.2018)
Current CEA: 9.8 as of 12.27.2018
MSS, KRAS wild type, BRAF wild type

Pyro
Posts: 57
Joined: Mon Oct 12, 2015 7:40 pm
Location: Tucson, AZ

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

Postby Pyro » Sat Feb 16, 2019 8:37 pm

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!
Aug 2015- Diag Stage 4 CC with mets to liver (38/m)
Sep 2015- Avastin/Folfox/Iron
Dec 2015-Not a surgery candidate for liver
Jan 2016- Erbitux/Folfiri, 2nd opinion at MDA in TX
Feb 2016 -MD Anderson liver surgery, Dr. Vauthey
Mar 2016 -30% of left lobe removed, PVE
May 2016 - 70% of liver removed
Jun 2016-Radiation
Jan 2017-permanent colost @ MDA
Jul 2017-Erb/FOLFURI
Nov 2017 -Lung & Liver ablations@MDA
Jan 2018 -Xeloda & Avastin mx
Jul 2018-Avast/FOLFURI
Sep 2018-Radiation
Chemo for life


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