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

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Jack&KatiesMommy
Posts: 521
Joined: Wed Dec 21, 2011 1:08 pm
Location: Columbus, OH

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

Postby Jack&KatiesMommy » Sun Aug 05, 2018 11:29 pm

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
Cynthia
Mommy to Jack (8) now (15) and Katie (4) now (11)
(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; 10/13; 12/13; 3/14; 8/14; 11/14; 2/15; 7/15; 12/15 RFA lungs
5/17: Upper Left Lobe of lung resected.
02/18: 3 new mets lymph nodes in hilar/lung:
05/18: Started Keytruda (MSS but moderate mutation burden): CEA: 66.4, 39.2, 23.8, 13, 3.5 NOW 1.8
08/18 Clear CT scan

stu
Posts: 901
Joined: Sat Aug 17, 2013 5:46 pm

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

Postby stu » Mon Aug 06, 2018 2:55 am

That is utterly amazing . You are pushing medical boundaries for sure.
So happy for you.
Stu
supporter to my mum who lives a great life despite a difficult diagnosis
stage4 2009 significant spread to liver
2010 colon /liver resection
chemo following recurrence
73% of liver removed
enjoying life treatment free
2016 lung resection
Oct 2017 nice clear scan . Two lung nodules disappeared
Oct 2018. Another clear scan .

plastikos
Posts: 309
Joined: Wed Jan 14, 2015 6:09 am

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

Postby plastikos » Mon Aug 06, 2018 8:34 am

Amazing news. Hoping for your continued response to Keytruda.
St. IV Colon CA @ 37, male, Kras wild, MSI-high (2014)
11/2014 Right Hemicolectomy + Liver Resection
12/2014 - 6/2015 FOLFOX + Cetuximab
10/2015 - Recurrence liver
Liver resection 10/2015
FOLFIRI 11/2015 - 5/2016
Recurrence liver, nodes 11/2016
Pembrolizumab started 12/2016 -> pseudoprogression(?) -> biliary obstruction -> biliary stenting
Chemo 4x: most mets inactive and smaller on PET-CT
March 2017 - Back on Pembrolizumab again
Sept 2017 - SIRT - > NED

boxhill
Posts: 125
Joined: Fri Apr 06, 2018 11:40 am

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

Postby boxhill » Mon Aug 06, 2018 10:52 am

Cynthia, this is great.

Is this something your health insurance will agree to pay for?
F, 64 at DX CRC Stage IV (or "3 1/2" per Dana Farber consult, LOL)
3/17/18 blockage, emergency surgery, r hemicolectomy
11 of 25 nodes
5 of 5 mesentery nodes, matted
0.5 cm sub-capsular liver met removed
pT3 pN2b pM1
Neg CEA, neg BRAF, KRAS G12D, germline mut ATM
dMMR, MSI-H, Neg for Lynch
5/4/18 FOLFOX
Added Neulasta 6/28/18
7/9/18 CT scans show no masses or enlarged nodes, 2mm indeterminate lung nodule
11/20/18 CT scans NED. Lung nodule likely calcified granuloma. Enlarged spleen.

crazylife
Posts: 255
Joined: Wed Dec 30, 2015 11:29 am

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

Postby crazylife » Mon Aug 06, 2018 12:30 pm

Such great news! Can someone tell me what this means? I can't tell if he has all of these or just the first two mentioned. This is from MSK-IMPACT:

Positive for the following somatic alterations in the clinically validated panel:

1. KRAS
2. TP53

Positive for the following somatic alterations in the investigational panel:

3. AMER1
4. APC
5. APC
6.PTEN
7. REL
Wife to DH, 41 years old, diagnosed 11/15
Stage 4, Mod diff, 13/24 LN, 1 liver met
Colon/liver resection at MSK, 11/15
8mm lung met (not confirmed) and enlarged lymph nodes 1/16
12 rounds of folfox (9 with Oxi) 6/16
NED - July 2016
NED - October 2016
3 lung mets - March 2017
7 lung mets, May 2017
RFA to largest met, June 2017
Lung mets growing slowly, October 2017 (off treatment since June 2016)
Right lung surgery, November 2017
Left lung surgery, January 2018
NED - May 2018

User avatar
Jack&KatiesMommy
Posts: 521
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 Aug 06, 2018 2:34 pm

boxhill wrote:Cynthia, this is great.

Is this something your health insurance will agree to pay for?


Great question. Yes, actually my insurance IS covering this treatment even though it is off-label for me due to my MSS status. However, my local oncologist submitted a request along with all of his data as well as that from Foundation One showing the correlation between mutation burden and Keytruda effectiveness that resulted in approval.

Cynthia
Cynthia
Mommy to Jack (8) now (15) and Katie (4) now (11)
(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; 10/13; 12/13; 3/14; 8/14; 11/14; 2/15; 7/15; 12/15 RFA lungs
5/17: Upper Left Lobe of lung resected.
02/18: 3 new mets lymph nodes in hilar/lung:
05/18: Started Keytruda (MSS but moderate mutation burden): CEA: 66.4, 39.2, 23.8, 13, 3.5 NOW 1.8
08/18 Clear CT scan

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Jack&KatiesMommy
Posts: 521
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 Aug 06, 2018 2:40 pm

crazylife wrote:Such great news! Can someone tell me what this means? I can't tell if he has all of these or just the first two mentioned. This is from MSK-IMPACT:

Positive for the following somatic alterations in the clinically validated panel:

1. KRAS
2. TP53

Positive for the following somatic alterations in the investigational panel:

3. AMER1
4. APC
5. APC
6.PTEN
7. REL


Unfortunately, I am not sure what this means. To my understanding, the Foundation One test is the only one that does mutation burden testing.
Cynthia
Cynthia
Mommy to Jack (8) now (15) and Katie (4) now (11)
(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; 10/13; 12/13; 3/14; 8/14; 11/14; 2/15; 7/15; 12/15 RFA lungs
5/17: Upper Left Lobe of lung resected.
02/18: 3 new mets lymph nodes in hilar/lung:
05/18: Started Keytruda (MSS but moderate mutation burden): CEA: 66.4, 39.2, 23.8, 13, 3.5 NOW 1.8
08/18 Clear CT scan

boswind
Posts: 40
Joined: Fri Apr 11, 2014 12:04 pm

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

Postby boswind » Thu Aug 09, 2018 9:40 pm

Great news! Thank you.

I contacted FoundationOne to get more information. For those who have advaced MSS colon cancer and have had targeted therapies for years, there is a chance that they have more gene mutations. Consequently, Keytruda may work for some of them. I am excited and will talk to my onc immediately.

The cost of the test is $5800 (listed price). The true price a insurance company will pay is likely:
Over $3000 if the testing sample is biopsy tissue and they will test 324 genes for mutations;
Under $2500 if the testing sample is peripheral blood and they test 62 genes for mutations.
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
70 rounds of chemos received (as of 03.2018)
Current CEA: 5.7
MSS, KRAS wild type, BRAF wild type

User avatar
Jack&KatiesMommy
Posts: 521
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 Aug 20, 2018 9:19 am

Boswind:
This is excellent follow-up with Foundation One. I hope that others are able to take advantage of this. Foundation One (and my local oncologist) are finding that Keytruda has been working for many patients outside the scope of the typical responders...primarily based on tumor mutation. This is an avenue that may be available to many who think that they have no other options.

My Oncologist prepared a request for my insurance including his and Foundation One's research regarding mutation burden and response and my insurance agreed to cover the cost of Keytruda even though it was an "off-label" use for me as an MSS patient.
Cynthia
Cynthia
Mommy to Jack (8) now (15) and Katie (4) now (11)
(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; 10/13; 12/13; 3/14; 8/14; 11/14; 2/15; 7/15; 12/15 RFA lungs
5/17: Upper Left Lobe of lung resected.
02/18: 3 new mets lymph nodes in hilar/lung:
05/18: Started Keytruda (MSS but moderate mutation burden): CEA: 66.4, 39.2, 23.8, 13, 3.5 NOW 1.8
08/18 Clear CT scan

Steph20021
Posts: 544
Joined: Sat Dec 27, 2014 4:58 pm
Location: Ontario, Canada

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

Postby Steph20021 » Fri Aug 24, 2018 11:31 pm

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?
DX 1/31/14 @ 33- SPS-T4a(invades visceral peri), N2a(6/106 LN), M1a(ovary) (Stage 4a) MSS; BRAF V600E mutation
2/1/14-subtotal col, lost R ovary, temp ileo
3/14-9/14- folfox; sepsis
11/14-CT/PET: L ovary met, pelvic met, (?)ghost liver met(?)
12/14-folfiri -13 rds kept me stable from 3/15-6/15
8/15-HIPEC, hysterectomy et al, 2nd temp ileo, NED?
09/15- cea 0.9
05/16- recurrence in abdo wall and lymph nodes
Jan/17- pulmonary embolism
Feb/17- 1 wk radiation to abdo wall
Aug/16- on folfiri
Jan/18-folfox

Steph20021
Posts: 544
Joined: Sat Dec 27, 2014 4:58 pm
Location: Ontario, Canada

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

Postby Steph20021 » Fri Aug 24, 2018 11:43 pm

It is amazing to me to see you doing so well 7 years out as a stage 4 patient!! It gives the rest of us hope!
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
DX 1/31/14 @ 33- SPS-T4a(invades visceral peri), N2a(6/106 LN), M1a(ovary) (Stage 4a) MSS; BRAF V600E mutation
2/1/14-subtotal col, lost R ovary, temp ileo
3/14-9/14- folfox; sepsis
11/14-CT/PET: L ovary met, pelvic met, (?)ghost liver met(?)
12/14-folfiri -13 rds kept me stable from 3/15-6/15
8/15-HIPEC, hysterectomy et al, 2nd temp ileo, NED?
09/15- cea 0.9
05/16- recurrence in abdo wall and lymph nodes
Jan/17- pulmonary embolism
Feb/17- 1 wk radiation to abdo wall
Aug/16- on folfiri
Jan/18-folfox

erinnatacha
Posts: 4
Joined: Tue Sep 20, 2016 2:22 pm

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

Postby erinnatacha » Tue Aug 28, 2018 5:49 pm

Amazing news!!!!

Steph20021
Posts: 544
Joined: Sat Dec 27, 2014 4:58 pm
Location: Ontario, Canada

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

Postby Steph20021 » Wed Aug 29, 2018 12:16 am

Heard back already from Foundation One. “ The price for our FoundationOne® test is $6193.60 CAD for patients of Canadian ordering physicians.“ However, it looks like there’s a trial still recruiting right now, and one location is at Princess Margaret Hospital in Toronto, it’s one of the OCTANE test trials, and while it doesn’t get everything that foundation one does, it’s free for us Canadians and I think it would be a good bet to do. I’ll be speaking with my oncology about this on Thursday. Hoping I can do it with a fresh biopsy on a current tumour.

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?
DX 1/31/14 @ 33- SPS-T4a(invades visceral peri), N2a(6/106 LN), M1a(ovary) (Stage 4a) MSS; BRAF V600E mutation
2/1/14-subtotal col, lost R ovary, temp ileo
3/14-9/14- folfox; sepsis
11/14-CT/PET: L ovary met, pelvic met, (?)ghost liver met(?)
12/14-folfiri -13 rds kept me stable from 3/15-6/15
8/15-HIPEC, hysterectomy et al, 2nd temp ileo, NED?
09/15- cea 0.9
05/16- recurrence in abdo wall and lymph nodes
Jan/17- pulmonary embolism
Feb/17- 1 wk radiation to abdo wall
Aug/16- on folfiri
Jan/18-folfox

Dionca
Posts: 19
Joined: Sat Dec 02, 2017 2:04 am

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

Postby Dionca » Wed Aug 29, 2018 12:42 am

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.
May 2015 right hemi CC cecum
removed terminal ileum, illeocecal valve, appendix, cecum, ascending colon, omentum
stage 3b T3 N1b MX 2/27 nodes (isolated tumour cells in 1 add'l node)
moderately differentiated
PNI - positive
LVI - positive
Folfox 12 sessions (oxi discontinued for 11 & 12)
Neulasta with 3-12 due to low WBC count
CEA at diagnosis 8.6
CEA after surgery 1.2
CEA during chemo 4.6 / 3.3 / 2.3
CEA after chemo 1.5 / 1.2 / 1.2 /1.2 /1.2 / 1.4 / 1.1 / 1.2 / 1.9 / 1.3 / 1.6 /1.4
neuropathy

Steph20021
Posts: 544
Joined: Sat Dec 27, 2014 4:58 pm
Location: Ontario, Canada

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

Postby Steph20021 » Wed Aug 29, 2018 5:01 pm

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.
DX 1/31/14 @ 33- SPS-T4a(invades visceral peri), N2a(6/106 LN), M1a(ovary) (Stage 4a) MSS; BRAF V600E mutation
2/1/14-subtotal col, lost R ovary, temp ileo
3/14-9/14- folfox; sepsis
11/14-CT/PET: L ovary met, pelvic met, (?)ghost liver met(?)
12/14-folfiri -13 rds kept me stable from 3/15-6/15
8/15-HIPEC, hysterectomy et al, 2nd temp ileo, NED?
09/15- cea 0.9
05/16- recurrence in abdo wall and lymph nodes
Jan/17- pulmonary embolism
Feb/17- 1 wk radiation to abdo wall
Aug/16- on folfiri
Jan/18-folfox


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