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

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Pyro
Posts: 230
Joined: Mon Oct 12, 2015 7:40 pm
Location: Tucson, AZ

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

Postby Pyro » Mon Apr 15, 2019 7:37 am

Well I get my 8 week blood test results today,probably followed my a scan. Cross your fingers, I don’t know what to do if it hasn’t worked.
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 -MDA liver surgery, Dr. Vauthey
Mar 2016 -30% of left lobe rem, PVE
May 2016 - 70% of liver rem
Jun 2016-Rad
Jan 2017-perm colost @MDA
Jul 2017-Erb/FOLFURI
Nov 2017 -Lung & Liver ablations@MDA
Jan 2018 -Xeloda & Avastin mx
Jul 2018-Avast/FOLFURI
Sep 2018-Rad
Mar 2019 - Keytruda, CEA @36, treatment failure

brokenwings
Posts: 62
Joined: Mon Jan 07, 2019 1:50 am

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

Postby brokenwings » Mon Apr 15, 2019 11:18 am

Fingers crossed, wishing you the best.
Keep us updated.

Big hug
DX January 2019
Adenocarcinoma - Sigmoid colon
Met to right ovary or borderline cyst?
Obstruction during hospital stay, just after colonoscopy. Emergency surgery. Temporary colostomy. Primary tumour still there (French protocol...)
Folfirinox: 4 cycles
CT Scan/PET Scan: ok for surgery
Surgery (CRS + HIPEC) scheduled for 04/29: let's hope my surgeon doesn't find any nasty surprises when he opens me up...
Nasty surprises found: peri mets all over my colon, irresectable.
2nd ptotocol: IP chemo + IV chemo.

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Jack&KatiesMommy
Posts: 582
Joined: Wed Dec 21, 2011 1:08 pm
Location: Columbus, OH

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

Postby Jack&KatiesMommy » Mon Apr 15, 2019 11:22 am

Praying for great results today!
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

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LPL
Posts: 624
Joined: Fri Apr 22, 2016 12:49 am
Location: Europe

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

Postby LPL » Mon Apr 15, 2019 11:38 am

Pyro wrote:Well I get my 8 week blood test results today,probably followed my a scan. Cross your fingers, I don’t know what to do if it hasn’t worked.

Best Wishes for you Pyro !
My fingers are crossed.
DH @ 65 DX 4/11/16 CC recto-sigmoid junction
Adenocarcenoma pt 35x15x9mm G3(biopsi) G1(surgical)
Mets 3 Liver resectable
T4aN1bM1a Stage IVa 2/9 LN
MSS, KRAS-mut G13D
CEA & CA19-9: 5/18 2.5 78 8/17 1.4 48 2/14/17 1.8 29
4 Folfox 6/15-7/30 (b4 liver surgery) 8 after
CT: 8/8 no change 3/27/17 NED->Jan-19 mets to lung
:!: Steroid induced hyperglycemia dx after 3chemo
Surgeries 2016: 3/18 Emergency colostomy
5/23 Primary+gallbl+stoma reversal+port 9/1 Liver mets
RFA 2019: Feb lung met

Pyro
Posts: 230
Joined: Mon Oct 12, 2015 7:40 pm
Location: Tucson, AZ

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

Postby Pyro » Mon Apr 15, 2019 3:00 pm

Well, it was 30. Didn’t expect that, went ahead with treatment. Thanks for thinking of me!
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 -MDA liver surgery, Dr. Vauthey
Mar 2016 -30% of left lobe rem, PVE
May 2016 - 70% of liver rem
Jun 2016-Rad
Jan 2017-perm colost @MDA
Jul 2017-Erb/FOLFURI
Nov 2017 -Lung & Liver ablations@MDA
Jan 2018 -Xeloda & Avastin mx
Jul 2018-Avast/FOLFURI
Sep 2018-Rad
Mar 2019 - Keytruda, CEA @36, treatment failure

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Jack&KatiesMommy
Posts: 582
Joined: Wed Dec 21, 2011 1:08 pm
Location: Columbus, OH

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

Postby Jack&KatiesMommy » Mon Apr 15, 2019 3:35 pm

Pyro:
It maybe on the downswing.....Mine did that a few times....it started to go up then stayed the same then went down. We thought that maybe it had continued to go up a bit then was coming down and we caught it on the downswing.

Next cycle will be telling. (Maybe you could ask your oncologist if you could get another CEA in say, 10 days....if you can't wait for 3 weeks. My oncologist did that for me at one point.)
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

boswind
Posts: 61
Joined: Fri Apr 11, 2014 12:04 pm

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

Postby boswind » Mon Apr 15, 2019 7:45 pm

@Pyro, good trend!
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
02.07.2018 - 03.06.2019, Centuximab + Irinotecan
90 rounds of chemos received (as of 12.27.18)
CEA: 9.8 as of 12.27.18
MSS, KRAS wild type, BRAF wild type
TMB = 12 mut/MB
03.14.2019 - Keytruda

natelaugh
Posts: 40
Joined: Wed Apr 03, 2019 11:40 pm

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

Postby natelaugh » Mon Apr 15, 2019 10:05 pm

Pyro, hope it works!!
Caregiver to 80M
DX:CC,RC,desc
11/2018 rightPain
1/19/19 scopy,path
1/23 CTscan
2/19 surgery
2/26-2/28 NGTube
2/28-3/14 TPN bc ileus
3/2 2nd surgeryCloseOpenWound
3/4-3/28 woundVac
size: 6cm Adenocarcinoma
grade Poorly
Stage IIIC T3N2aMx
PositiveLymph:5of28
BaselineCEA:68
LVI:Y
PNI:N
Surgical margins:clear
MSI:MMR (MLH1, MSH2, MSH6, PMS2) Intact nuclear expression
Lynch status:N
Laparascopic, partial colectomy
CEA:3/28/19 2.8
Chemo:4/16/19-9/17/19 5FU,12cycles,every 14days,leucoverin,zofran,Dexamethasone

Pyro70
Posts: 94
Joined: Mon Jan 21, 2019 4:25 pm

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

Postby Pyro70 » Tue Apr 16, 2019 11:56 pm

Pyro wrote:Well, it was 30. Didn’t expect that, went ahead with treatment. Thanks for thinking of me!


Pyro, if you need more encouragement I recently heard Dr. Bekaii-Saab (who seems like one of the smartest CRC oncs to me) say that TMB is likely more important than MSI status.

And high tumor mutation burden I think is a much better predictor at the end of the day of response versus MSI-high on its own. So I think MSI-high is just a surrogate


https://www.onclive.com/inside-oncology/practical-approach-treatment-mCRC/refinement-of-techniques-and-the-future-of-mcrc

I think you’re on the right path. I hope your immune system is setting those rogue cells ablaze right now. Remember, immunotherapy can take a while to ramp up.

Best
Dx Jan 2017 stage IVB w/ PC age 35
FOLFOX
SEP 17 HIPEC 1, anastamosis leak
XELODA
MAR 18 HIPEC 2
JUN 18, ileo reversal and 2nd anastamosis leak

Pyro
Posts: 230
Joined: Mon Oct 12, 2015 7:40 pm
Location: Tucson, AZ

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

Postby Pyro » Wed Apr 17, 2019 7:49 am

Thank you for the encouragement, it makes sense but I’m no scientist. My oncologist told me he was surprised, expecting a large jump in CEA, Awesome.
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 -MDA liver surgery, Dr. Vauthey
Mar 2016 -30% of left lobe rem, PVE
May 2016 - 70% of liver rem
Jun 2016-Rad
Jan 2017-perm colost @MDA
Jul 2017-Erb/FOLFURI
Nov 2017 -Lung & Liver ablations@MDA
Jan 2018 -Xeloda & Avastin mx
Jul 2018-Avast/FOLFURI
Sep 2018-Rad
Mar 2019 - Keytruda, CEA @36, treatment failure

behconsult
Posts: 245
Joined: Fri Jul 04, 2014 4:53 pm

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

Postby behconsult » Wed Apr 17, 2019 8:01 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 MSS 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 last 7 years) my MSS 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


Cynthia, If I might add, I think it is amazing kindness and compassion that you reach out to members and educate them about this. Even I spoke with my onc about your posting. I am low mutation unfortunately, but many are not. Thank you
Stage 4 Age 56 BrafV660E 5/14
spot on perit/ Right side tumor
Resctn 6/9/2014
Folfox strt 7/2014. 6 of 12 tx
Chemo induced DM2
Pet 4 mets to lung (1 cm, 6 mm) Xeloda/Avastin 9/16 to present.
Cryo-ablation to four spots- Collapsed lung/chest tube 2x
Possible local recurrence in a spot or two on PET. Stable CT

Pyro
Posts: 230
Joined: Mon Oct 12, 2015 7:40 pm
Location: Tucson, AZ

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

Postby Pyro » Wed Apr 17, 2019 8:19 am

Jack&KatiesMommy wrote:Pyro:
It maybe on the downswing.....Mine did that a few times....it started to go up then stayed the same then went down. We thought that maybe it had continued to go up a bit then was coming down and we caught it on the downswing.

Next cycle will be telling. (Maybe you could ask your oncologist if you could get another CEA in say, 10 days....if you can't wait for 3 weeks. My oncologist did that for me at one point.)
Cynthia

Thanks for your help, are your scans good as well? We’re you showing any activity when your CEA was high? My scan is mid-May. I don’t think I’ll get a CEA test 11 days early, it not like I really want to do chemo if it went up anyway, maybe not ever again.
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 -MDA liver surgery, Dr. Vauthey
Mar 2016 -30% of left lobe rem, PVE
May 2016 - 70% of liver rem
Jun 2016-Rad
Jan 2017-perm colost @MDA
Jul 2017-Erb/FOLFURI
Nov 2017 -Lung & Liver ablations@MDA
Jan 2018 -Xeloda & Avastin mx
Jul 2018-Avast/FOLFURI
Sep 2018-Rad
Mar 2019 - Keytruda, CEA @36, treatment failure

User avatar
Jack&KatiesMommy
Posts: 582
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 Apr 17, 2019 8:54 am

behconsult wrote:
Cynthia, If I might add, I think it is amazing kindness and compassion that you reach out to members and educate them about this. Even I spoke with my onc about your posting. I am low mutation unfortunately, but many are not. Thank you


BUT....my oncologist said that if they had tested my original tumor (or even after 1-2 years of treatment) I may have been identified as having a low mutation burden. My oncologist believes that my MSS high Mutation Burden may be due in fact to all of the years of many different treatments and changes that occurred in the colon cancer in response to those treatments. I don't know what tumor tissue they sampled when they measured your TMB...but if it wasn't from a recent sample....I would wonder if it accurately reflects the current TMB of your cancer now.

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

Pyro70
Posts: 94
Joined: Mon Jan 21, 2019 4:25 pm

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

Postby Pyro70 » Wed Apr 17, 2019 10:51 am

Jack&KatiesMommy wrote:
behconsult wrote:
Cynthia, If I might add, I think it is amazing kindness and compassion that you reach out to members and educate them about this. Even I spoke with my onc about your posting. I am low mutation unfortunately, but many are not. Thank you


BUT....my oncologist said that if they had tested my original tumor (or even after 1-2 years of treatment) I may have been identified as having a low mutation burden. My oncologist believes that my MSS high Mutation Burden may be due in fact to all of the years of many different treatments and changes that occurred in the colon cancer in response to those treatments. I don't know what tumor tissue they sampled when they measured your TMB...but if it wasn't from a recent sample....I would wonder if it accurately reflects the current TMB of your cancer now.

Cynthia


That’s interesting. Pyro, how old was the tissue you had sequenced for TMB?

Thanks
Dx Jan 2017 stage IVB w/ PC age 35
FOLFOX
SEP 17 HIPEC 1, anastamosis leak
XELODA
MAR 18 HIPEC 2
JUN 18, ileo reversal and 2nd anastamosis leak

Pyro
Posts: 230
Joined: Mon Oct 12, 2015 7:40 pm
Location: Tucson, AZ

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

Postby Pyro » Thu Apr 18, 2019 7:40 am

Pyro70 wrote:
Jack&KatiesMommy wrote:
behconsult wrote:
Cynthia, If I might add, I think it is amazing kindness and compassion that you reach out to members and educate them about this. Even I spoke with my onc about your posting. I am low mutation unfortunately, but many are not. Thank you


BUT....my oncologist said that if they had tested my original tumor (or even after 1-2 years of treatment) I may have been identified as having a low mutation burden. My oncologist believes that my MSS high Mutation Burden may be due in fact to all of the years of many different treatments and changes that occurred in the colon cancer in response to those treatments. I don't know what tumor tissue they sampled when they measured your TMB...but if it wasn't from a recent sample....I would wonder if it accurately reflects the current TMB of your cancer now.

Cynthia


That’s interesting. Pyro, how old was the tissue you had sequenced for TMB?

Thanks


My oncologist told me exactly what JKM was told about tumors changing over time, my samples were from my major colostomy procedure. I had been through a couple of surgeries and countless chemos by that point. Things could have changed, it’s a sample from Jan 2017.
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 -MDA liver surgery, Dr. Vauthey
Mar 2016 -30% of left lobe rem, PVE
May 2016 - 70% of liver rem
Jun 2016-Rad
Jan 2017-perm colost @MDA
Jul 2017-Erb/FOLFURI
Nov 2017 -Lung & Liver ablations@MDA
Jan 2018 -Xeloda & Avastin mx
Jul 2018-Avast/FOLFURI
Sep 2018-Rad
Mar 2019 - Keytruda, CEA @36, treatment failure


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