KRAS G12V Mutation Question

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Sharing Hope
Posts: 6
Joined: Wed Oct 25, 2017 5:02 am

KRAS G12V Mutation Question

Postby Sharing Hope » Mon Nov 06, 2017 10:45 pm

Hi, everyone~

I just joined the club and I'm so impressed by everyone's courage and helpfulness in this forum.

I've learned I have the KRAS G12V mutation and just wanted to hear from members who have the same mutation and their experience in responsiveness to FOLFOX or FOLFIRI (incl 5FU). The research I'm seeing is, honestly, pretty grim for this specific mutation allowing these therapies to reduce tumor (cure) and "clean up" rogue cells to prevent future tumor growth.

Any success stories?

I'd love your helpful feedback as I navigate my treatment options.

Thank you, ever so much.
Happy Mama w/2 Sons/Smitten Wife since 1988; BD/1968; Lifelong vegetarian; Non-smoker/drinker; 5'7.5" H/130 lbs
6/16 Baseline Colonoscopy; Sessile polyps - adenocarcinoma near Splenic Flexure; CEA .8
8/16 Robotic colon resection of Descending Colon; 30 LN clear; Stage 1
9/17 Liver tumor found/abdominal pain; CEA 16.4; Stage 4
9/17-11/17 FOLFOX/5FU + Avastin
11/17 CEA 6
MSS - KRAS G12V Mutation
Hepatic resection of left liver lobe scheduled 12/17 (pending decent CT)
Chemo scheduled 2/18 - 4/18

NHMike
Posts: 696
Joined: Fri Jul 21, 2017 3:43 am

Re: KRAS G12V Mutation Question

Postby NHMike » Tue Nov 07, 2017 3:10 am

Fascinating post.

I dug out my tumor genomic analysis email and it appears that I am KRAS G12D. I read up on your variant and mine and it looks like we both won’t benefit from drugs that attack EGFR growth and these are Cetuximap (Erbitux) and Panitumumap (Vectibix). We can still make use of drugs that target VEGF and there’s always 5FU and oxiliplatin.

FOLFOX has 5FU, Oxipilatin and leucovorin and those aren't indicated as not working on our mutations.
FOLFIRI has 5FU, leucovorin and Irinotecan and those aren't indicated as not work on our mutations.

I just found a Clinical Trials page for KRAS G12D at Mass General. It describes CRC, KRAS and my variant. It also lists clinical trials for it for treatment. They do a very nice job gathering a lot of information in one place.
Last edited by NHMike on Tue Nov 07, 2017 7:36 am, edited 3 times in total.
6/23/17: ER rectal bleeding; Colonoscopy+Biopsy
7/13: Stage 3B rectal cancer. T3, N1b, M0. 5.2 x 4.5 x 4.3 cm. Lymphs: 6 x 4 mm, 8 x 6 mm, 5 x 5 mm
7/31-9/8: Xeloda 3,400 mg/day+radiation
7/5: CEA 2.7; 8/16: 1.9; 9/8: 1.8. 11/30: 0.6
MSS, KRAS G12D
10/6: 2.7 x 2.2 x 1.6 cm (-90%). Lymphs: 3 x 3 mm (-62.5%), 4 x 3 mm (-75%), 5 x 3 mm (-40%). 5.1 CM from AV
10/30: Surgery: LAR, Temp Ileostomy
Path report: Tumor regression grade: 0 (complete response).

Sharing Hope
Posts: 6
Joined: Wed Oct 25, 2017 5:02 am

Re: KRAS G12V Mutation Question

Postby Sharing Hope » Tue Nov 07, 2017 6:52 am

NHMike wrote:Fascinating post.
We can still make use if drugs that target VEGF and there’s always 5FU and oxiliplatin.

_____________________________________
Thank you so much for your reply, NHMike! Could you help me know where/how you learned about 5FU/Oxiliplatin is effective? I have a very large, contained liver tumor hoping to shrink for surgery. Throughout my chemo treatment on FOLFOX they've had to keep reducing agents because I'm so "special." Evidently, I've rec'd all side effects to the point of not being able to eat or continue my normal life routine. It's gotten a little more doable after a week past treatment, but as I've dug into online research articles about KRAS G12v, I'm not encouraged to keep going this route. To me, it's not worth a shooting chemo in the dark when I could be looking at other options..

Anyone else know if their cancer has a KRAS G12v mutation and effectiveness with FOLFOX or FOLFIRI?

Thank you, again!
Happy Mama w/2 Sons/Smitten Wife since 1988; BD/1968; Lifelong vegetarian; Non-smoker/drinker; 5'7.5" H/130 lbs
6/16 Baseline Colonoscopy; Sessile polyps - adenocarcinoma near Splenic Flexure; CEA .8
8/16 Robotic colon resection of Descending Colon; 30 LN clear; Stage 1
9/17 Liver tumor found/abdominal pain; CEA 16.4; Stage 4
9/17-11/17 FOLFOX/5FU + Avastin
11/17 CEA 6
MSS - KRAS G12V Mutation
Hepatic resection of left liver lobe scheduled 12/17 (pending decent CT)
Chemo scheduled 2/18 - 4/18

User avatar
DH2Sleen
Posts: 68
Joined: Thu Jan 29, 2015 10:10 am

Re: KRAS G12V Mutation Question

Postby DH2Sleen » Tue Nov 07, 2017 7:23 am

Hi Sharing Hope,
You are right that chemo options are limited in Kras mutations. It would be helpful to have more of your story. Please add a signature so we know something about your treatment history.
In general, if you are stage III or IV, you would need to get initial treatment with standard therapy. Find out about your micro-satellite status (MSI-H or MSS). If your doctor doesn't know about trials targeting your mutations or MS status, your need to get a second opinion from a major cancer hospital.
There is currently one immunotherapy trail that targets G12V, but it requires a particular HLA match (think of it as an organ donor match). This trial requires that patients have tried standard-of-care treatment before applying.
Things are changing rapidly and new trails keep coming out. Keep reading on this site and educate yourself. You are your best advocate.
DW, Sleen dx 9/2013 @47yo: IIIc T4b N2b MX
09/2013 colectomy
10/2013 - 3/2014 FOLFOX
04/2014 - 6/2014 Rad to bladder
12/2014 +'ve for lung mets, MX becomes M1
03/2015 enter TIL trial @ NIH
07/01/15 Receive 148E9 cells to target K-ras G12D mutation
08/11/15 Reduction=18%, no new tumors
09/15/15 25%
10/20/15 27%; PET -> one hot met
11/24/15 30% all mets shrinking
01/26/16 46% but one suspicious met
03/24/16 46% but one growing
04/07/16 Lung lobectomy NED for the first time

NHMike
Posts: 696
Joined: Fri Jul 21, 2017 3:43 am

Re: KRAS G12V Mutation Question

Postby NHMike » Tue Nov 07, 2017 7:39 am

Colorectal KRAS G12V page at MGH Targeted Cancer Care Pages

This is a fantastic page for getting details on your cancer variations. Wish I had known about it a lot sooner. I don't know whether or not it would have mattered as far as treatment goes but it would have answered the nagging question of am I doing all that I can?

https://targetedcancercare.massgeneral. ... V-(c-35G-T).aspx
6/23/17: ER rectal bleeding; Colonoscopy+Biopsy
7/13: Stage 3B rectal cancer. T3, N1b, M0. 5.2 x 4.5 x 4.3 cm. Lymphs: 6 x 4 mm, 8 x 6 mm, 5 x 5 mm
7/31-9/8: Xeloda 3,400 mg/day+radiation
7/5: CEA 2.7; 8/16: 1.9; 9/8: 1.8. 11/30: 0.6
MSS, KRAS G12D
10/6: 2.7 x 2.2 x 1.6 cm (-90%). Lymphs: 3 x 3 mm (-62.5%), 4 x 3 mm (-75%), 5 x 3 mm (-40%). 5.1 CM from AV
10/30: Surgery: LAR, Temp Ileostomy
Path report: Tumor regression grade: 0 (complete response).

Sharing Hope
Posts: 6
Joined: Wed Oct 25, 2017 5:02 am

Re: KRAS G12V Mutation Question

Postby Sharing Hope » Tue Nov 07, 2017 8:03 am

Thank you, NHMike--

I agree with learning all we can about our particular, specific, DNA so that we're not ignorant about treatment options. Oncologists are doing the best they can - but we need to weigh out the costs if chemo affects quality of our lives. Ya know?

Thank you, DH2Sleen--

My signature is now included for a better view on "me." Thank you for your kind help!
Happy Mama w/2 Sons/Smitten Wife since 1988; BD/1968; Lifelong vegetarian; Non-smoker/drinker; 5'7.5" H/130 lbs
6/16 Baseline Colonoscopy; Sessile polyps - adenocarcinoma near Splenic Flexure; CEA .8
8/16 Robotic colon resection of Descending Colon; 30 LN clear; Stage 1
9/17 Liver tumor found/abdominal pain; CEA 16.4; Stage 4
9/17-11/17 FOLFOX/5FU + Avastin
11/17 CEA 6
MSS - KRAS G12V Mutation
Hepatic resection of left liver lobe scheduled 12/17 (pending decent CT)
Chemo scheduled 2/18 - 4/18

Sharing Hope
Posts: 6
Joined: Wed Oct 25, 2017 5:02 am

Re: KRAS G12V Mutation Question

Postby Sharing Hope » Tue Nov 07, 2017 8:31 am

Thank you, NHMike!

Indeed it's important to know our specific tumor DNA to understand value or responsiveness of targeted therapies. I'm weighing quality of life with side effects right now and need to know how effective FOLFOX/FOLFIRI are for others with same mutation.

I enjoy searching through research articles, but I'm not finding encouraging information.

To other members - if you don't know your current tumor DNA, please ask your oncologist? If you have same KRAS G12V (not wild type or other 12 or 13 codons), or know of someone with this same DNA mutation, please reply with your experience? It would be so helpful to me.

Thank you, so much.
Happy Mama w/2 Sons/Smitten Wife since 1988; BD/1968; Lifelong vegetarian; Non-smoker/drinker; 5'7.5" H/130 lbs
6/16 Baseline Colonoscopy; Sessile polyps - adenocarcinoma near Splenic Flexure; CEA .8
8/16 Robotic colon resection of Descending Colon; 30 LN clear; Stage 1
9/17 Liver tumor found/abdominal pain; CEA 16.4; Stage 4
9/17-11/17 FOLFOX/5FU + Avastin
11/17 CEA 6
MSS - KRAS G12V Mutation
Hepatic resection of left liver lobe scheduled 12/17 (pending decent CT)
Chemo scheduled 2/18 - 4/18

NHMike
Posts: 696
Joined: Fri Jul 21, 2017 3:43 am

Re: KRAS G12V Mutation Question

Postby NHMike » Tue Nov 07, 2017 2:30 pm

Sharing Hope wrote:Thank you, NHMike!

Indeed it's important to know our specific tumor DNA to understand value or responsiveness of targeted therapies. I'm weighing quality of life with side effects right now and need to know how effective FOLFOX/FOLFIRI are for others with same mutation.

I enjoy searching through research articles, but I'm not finding encouraging information.

To other members - if you don't know your current tumor DNA, please ask your oncologist? If you have same KRAS G12V (not wild type or other 12 or 13 codons), or know of someone with this same DNA mutation, please reply with your experience? It would be so helpful to me.

Thank you, so much.


I think that you have part of your answer in your signature. Your chemo decreased your CEA and shrunk your tumor to where it can be operated on. For me, my neo-adjuvant chemo and radiation reduced the tumor from 100+ cm^3 to under 10 cm^3 or reduced it by 90%.

I had Xeloda (oral 5FU) and radiation therapy up-front and had surgery to remove the tumor last week. So I will have mop-up chemo, probably starting within the next month. It's also important to me as to what chemo is used. As far as I'm aware, though, it's only the Anti-EGFR drugs that have been shown to be ineffective with our variants.

Genomic tumor testing is not automatic for cancer patients. It may even be that most don't patients get it. It wasn't part of my care plan though I did request it from my oncologist. I think that the testing costs about $1,000 these days and insurance may not cover it if they think that you're in for a standard course of treatment. For CRC, the MSI-H/Lynch stuff can be determined by the cheaper Immunohistochemistry test which is what they did for me. I only got Genomic Tumor Testing because my son's manager offered to do it for me. I suspect that some hospitals do it automatically but I'd guess that most don't and that it would have to be justified to insurance. I do think that it should be included in the standard of care as there are some mutations where it could be dangerous if the doctors didn't know about them.
6/23/17: ER rectal bleeding; Colonoscopy+Biopsy
7/13: Stage 3B rectal cancer. T3, N1b, M0. 5.2 x 4.5 x 4.3 cm. Lymphs: 6 x 4 mm, 8 x 6 mm, 5 x 5 mm
7/31-9/8: Xeloda 3,400 mg/day+radiation
7/5: CEA 2.7; 8/16: 1.9; 9/8: 1.8. 11/30: 0.6
MSS, KRAS G12D
10/6: 2.7 x 2.2 x 1.6 cm (-90%). Lymphs: 3 x 3 mm (-62.5%), 4 x 3 mm (-75%), 5 x 3 mm (-40%). 5.1 CM from AV
10/30: Surgery: LAR, Temp Ileostomy
Path report: Tumor regression grade: 0 (complete response).

NHMike
Posts: 696
Joined: Fri Jul 21, 2017 3:43 am

Re: KRAS G12V Mutation Question

Postby NHMike » Tue Nov 07, 2017 3:20 pm

I did find a clinical trial for a drug for KRAS G12D but I don’t qualify for the trial as I’m not Stage 4 with an unresectable tumor. That’s okay though as I think that the standard treatment is working well.
6/23/17: ER rectal bleeding; Colonoscopy+Biopsy
7/13: Stage 3B rectal cancer. T3, N1b, M0. 5.2 x 4.5 x 4.3 cm. Lymphs: 6 x 4 mm, 8 x 6 mm, 5 x 5 mm
7/31-9/8: Xeloda 3,400 mg/day+radiation
7/5: CEA 2.7; 8/16: 1.9; 9/8: 1.8. 11/30: 0.6
MSS, KRAS G12D
10/6: 2.7 x 2.2 x 1.6 cm (-90%). Lymphs: 3 x 3 mm (-62.5%), 4 x 3 mm (-75%), 5 x 3 mm (-40%). 5.1 CM from AV
10/30: Surgery: LAR, Temp Ileostomy
Path report: Tumor regression grade: 0 (complete response).

sdino
Posts: 44
Joined: Tue Mar 28, 2017 5:32 pm

Re: KRAS G12V Mutation Question

Postby sdino » Wed Nov 08, 2017 7:58 am

Hi NHMike - Quick question , What Clinical Trial are you referring to in relationship with KRAS G12D ?
thanks,
Caregiver for Wife 52 yrs old
DX:11/16-CC sigmoid colon 3 cm, Lung Adenocarcinoma Stg IV
Mets: 1.2 cm now 7 mm lung w/14 other nodules less than 6 mm. 7/17 growth in Mets
MSS, KRAS-mut G12D; TP53;
Completed 12 rounds Folfox/Avastin + Oxi 11/16 to 5/17
8/17 Start Xeloda + Avastin
CT Scans: 11/16; 1/17 lung mets/colon shrinkage; 5/17 colon & lung met shrinkage, 7/17 and 11/17 disease progression lungs/colon
CEA: 16 - 11/16; 4 – 12/16; 0.5 – 2/17; 0.6 - 5/17; 2.6 - 7/17; 10/17 - 1.9, 11/17 - 2.6

NHMike
Posts: 696
Joined: Fri Jul 21, 2017 3:43 am

Re: KRAS G12V Mutation Question

Postby NHMike » Wed Nov 08, 2017 8:17 am

https://clinicaltrials.gov/ct2/show/NCT02079740

BTW, this looks like it's for G12*, not just G12D. It also is for codons 13, 61, and 146. I had a look at the drugs under trial and did not see how they affect KRAS (and NRAS too) tumors but I'm not a bio guy.
6/23/17: ER rectal bleeding; Colonoscopy+Biopsy
7/13: Stage 3B rectal cancer. T3, N1b, M0. 5.2 x 4.5 x 4.3 cm. Lymphs: 6 x 4 mm, 8 x 6 mm, 5 x 5 mm
7/31-9/8: Xeloda 3,400 mg/day+radiation
7/5: CEA 2.7; 8/16: 1.9; 9/8: 1.8. 11/30: 0.6
MSS, KRAS G12D
10/6: 2.7 x 2.2 x 1.6 cm (-90%). Lymphs: 3 x 3 mm (-62.5%), 4 x 3 mm (-75%), 5 x 3 mm (-40%). 5.1 CM from AV
10/30: Surgery: LAR, Temp Ileostomy
Path report: Tumor regression grade: 0 (complete response).

NHMike
Posts: 696
Joined: Fri Jul 21, 2017 3:43 am

Re: KRAS G12V Mutation Question

Postby NHMike » Wed Nov 08, 2017 9:40 pm

Good overview paper on KRAS. It gets a bit into the weeds and you need some genetics and biology to read it (unless you can wing it) but I think that it covers the problems with KRAS, which drugs don't work or can make cancer worse, and avenues for further targeted therapies. I passed it to my son to read. KRAS is 35-40% of CRC tumors so I'd guess that a lot of folks here have KRAS variants but I'd guess that most don't know it because they aren't tested for it.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4372129/

"Mutations in the KRAS oncogene represent one of the most prevalent genetic alterations in colorectal cancer (CRC), the third leading cause of cancer-related death in the US. In addition to their well-characterized function in driving tumor progression, KRAS mutations have been recognized as a critical determinant of the therapeutic response of CRC. Recent studies demonstrate that KRAS-mutant tumors are intrinsically insensitive to clinically-used epidermal growth factor receptor (EGFR) targeting antibodies, including cetuximab and panitumumab. Acquired resistance to the anti-EGFR therapy was found to be associated with enrichment of KRAS-mutant tumor cells. However, the underlying molecular mechanism of mutant-KRAS-mediated therapeutic resistance has remained unclear. Despite intensive efforts, directly targeting mutant KRAS has been largely unsuccessful. This review summarizes the recent advances in understanding the biological function of KRAS mutations in determining the therapeutic response of CRC, highlighting several recently developed agents and strategies for targeting mutant KRAS, such as synthetic lethal interactions."
6/23/17: ER rectal bleeding; Colonoscopy+Biopsy
7/13: Stage 3B rectal cancer. T3, N1b, M0. 5.2 x 4.5 x 4.3 cm. Lymphs: 6 x 4 mm, 8 x 6 mm, 5 x 5 mm
7/31-9/8: Xeloda 3,400 mg/day+radiation
7/5: CEA 2.7; 8/16: 1.9; 9/8: 1.8. 11/30: 0.6
MSS, KRAS G12D
10/6: 2.7 x 2.2 x 1.6 cm (-90%). Lymphs: 3 x 3 mm (-62.5%), 4 x 3 mm (-75%), 5 x 3 mm (-40%). 5.1 CM from AV
10/30: Surgery: LAR, Temp Ileostomy
Path report: Tumor regression grade: 0 (complete response).

sdino
Posts: 44
Joined: Tue Mar 28, 2017 5:32 pm

Re: KRAS G12V Mutation Question

Postby sdino » Thu Nov 09, 2017 9:57 am

Thanks for the Info NHMike ! Cheers !
Caregiver for Wife 52 yrs old
DX:11/16-CC sigmoid colon 3 cm, Lung Adenocarcinoma Stg IV
Mets: 1.2 cm now 7 mm lung w/14 other nodules less than 6 mm. 7/17 growth in Mets
MSS, KRAS-mut G12D; TP53;
Completed 12 rounds Folfox/Avastin + Oxi 11/16 to 5/17
8/17 Start Xeloda + Avastin
CT Scans: 11/16; 1/17 lung mets/colon shrinkage; 5/17 colon & lung met shrinkage, 7/17 and 11/17 disease progression lungs/colon
CEA: 16 - 11/16; 4 – 12/16; 0.5 – 2/17; 0.6 - 5/17; 2.6 - 7/17; 10/17 - 1.9, 11/17 - 2.6

Sharing Hope
Posts: 6
Joined: Wed Oct 25, 2017 5:02 am

Re: KRAS G12V Mutation Question

Postby Sharing Hope » Thu Nov 09, 2017 10:10 am

Thank you, so much, for all your time and helpful posts, NHMike!

I didn't realize that tumor mutation testing isn't protocol - wow. Pretty critical in treatment plans, I'd say.

Glad to hear you had a successful surgery. How is your recovery? Was it laporoscopic?

Though my surgery is scheduled, they wanted to shrink my tumor with chemo - it's on the large side 2+". It hasn't shrunk but they'll take out my entire left lobe.

I hope your recuperation continues to go well and you beat this fully!

Cheers!
Happy Mama w/2 Sons/Smitten Wife since 1988; BD/1968; Lifelong vegetarian; Non-smoker/drinker; 5'7.5" H/130 lbs
6/16 Baseline Colonoscopy; Sessile polyps - adenocarcinoma near Splenic Flexure; CEA .8
8/16 Robotic colon resection of Descending Colon; 30 LN clear; Stage 1
9/17 Liver tumor found/abdominal pain; CEA 16.4; Stage 4
9/17-11/17 FOLFOX/5FU + Avastin
11/17 CEA 6
MSS - KRAS G12V Mutation
Hepatic resection of left liver lobe scheduled 12/17 (pending decent CT)
Chemo scheduled 2/18 - 4/18

NHMike
Posts: 696
Joined: Fri Jul 21, 2017 3:43 am

Re: KRAS G12V Mutation Question

Postby NHMike » Thu Nov 09, 2017 10:53 am

Sharing Hope wrote:Thank you, so much, for all your time and helpful posts, NHMike!

I didn't realize that tumor mutation testing isn't protocol - wow. Pretty critical in treatment plans, I'd say.

Glad to hear you had a successful surgery. How is your recovery? Was it laporoscopic?

Though my surgery is scheduled, they wanted to shrink my tumor with chemo - it's on the large side 2+". It hasn't shrunk but they'll take out my entire left lobe.

I hope your recuperation continues to go well and you beat this fully!

Cheers!


My surgery was Laparoscopic Assisted LAR so it was an open surgery and the surgeon indicated this in the pre-op meeting. So recovery is a lot slower than I'd like but I was able to take a 0.6 mile walk this morning (normal days I may walk/run 5-10 miles).

2 inches is definitely large and it's going to put pressure on something. I had some pain from mine which was over 100 cm^3 or over 6 in^3 and I had this fear that I wasn't going to be able to go to the bathroom at all because it was getting so big. I can understand the worries about a large tumor.

Some ideas for papers that I thought up this morning:

* It would be interesting to write a paper to make the case for Genomic Tumor Testing on Colorectal biopsies for Rectal Cancer or tumors for Colon Cancer. The case could be made for patients with KRAS so that they shouldn't use Anti-EGFR drugs and BRAF so that oncologists know that there is time pressure and that they're dealing with an aggressive cancer that may not respond well to traditional front-line chemotherapy.

* It would also be interesting to write a paper describing all of the known mutations of Colorectal Cancer, their prevalence, survival rates, response to front-line Colorectal Cancer chemotherapy and targeted therapies. Depth would be a variable for the paper. It could go into the technical details of how the mutations and variants work or it could just be upper-level numbers. Or there could be two papers overall, one with statistics and the other describing the mechanisms of the know Colorectal Cancer mutations.

I will keep an eye out for your comments as your surgery date approaches.
6/23/17: ER rectal bleeding; Colonoscopy+Biopsy
7/13: Stage 3B rectal cancer. T3, N1b, M0. 5.2 x 4.5 x 4.3 cm. Lymphs: 6 x 4 mm, 8 x 6 mm, 5 x 5 mm
7/31-9/8: Xeloda 3,400 mg/day+radiation
7/5: CEA 2.7; 8/16: 1.9; 9/8: 1.8. 11/30: 0.6
MSS, KRAS G12D
10/6: 2.7 x 2.2 x 1.6 cm (-90%). Lymphs: 3 x 3 mm (-62.5%), 4 x 3 mm (-75%), 5 x 3 mm (-40%). 5.1 CM from AV
10/30: Surgery: LAR, Temp Ileostomy
Path report: Tumor regression grade: 0 (complete response).


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