Calling all those on anti-EGFR therapies

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mpbser
Posts: 953
Joined: Wed Apr 19, 2017 11:52 am

Calling all those on anti-EGFR therapies

Postby mpbser » Fri Feb 15, 2019 3:25 pm

TWO QUESTIONS:

For those who are on, or have been on, an anti-EGFR therapy, obviously you are KRAS-wild or else it would not have been prescribed for you. But was your cancer ever determined to be EGFR-expressing (technically overexpressing and aka EGFR-positive)?

Now that my husband is embarking on second-line therapies, I am exploring all options available. His Oncopanel report does not show that he has an EGFR mutation, but there is one EGFR-related notation: copy number variant 7 Chromosomal level Gain EGFR. I wonder if this puts his tumor in the EGFR-expressing category. Anyone have any idea?
Wife 4/17 Dx age 45
5/17 LAR
Adenocarcinoma
low grade
1st primary T3 N2b M1a
Stage IVA
8/17 Sub-total colectomy
2nd primary 5.5 cm T1 N0
9 of 96 nodes
CEA: < 2.9
MSS
Lynch no; KRAS wild
Immunohistochemsistry Normal
Fall 2017 FOLFOX shrank the 1 met in liver
1/18 Liver left hepatectomy seg 4
5/18 CT clear
12/18 MRI 1 liver met
3/7/19 Resection & HAI
4/1/19 Folfiri & FUDR
5/13/19 HAI pump catheter dislodge, nearly bled to death
6-7 '19 5FU 4 cycles
NED

User avatar
GrouseMan
Posts: 888
Joined: Mon Aug 12, 2013 12:30 pm
Location: SE Michigan USA

Re: Calling all those on anti-EGFR therapies

Postby GrouseMan » Fri Feb 15, 2019 5:06 pm

His tumors over express EGFr according to this. So its over producing the receptor and EGF protein around slips into it and turns it on. Its a driver of tumor growth. Thus inhibition of EGFr slows growth. If they use Erbitux it will work for a while and likely well. But eventually Erbitux starts to fail usually because the tumor finds another way to turn the EGFr receptor on by over producing closely related proteins that will also activate similar closely related ErbB's that take over the driving of growth. It doesn't require a mutation. Just extra copies. But there have been studies that show that when Erbitux fails one can quit it for a while and the tumor will revert back to becoming sensitive to it again or other similar small molecule inhibitors of EGFr. The new generation of EGFr inhibitors not only work against over expression but some also work on the mutant variants and the additional ErbB's. There are more drugs approved against EGFr for use in Lung Cancer than Colon cancer, but they should work in colon cancer as well if one can do Erbitux the others are likely to be effective also.

Here is some information about Erbitux:
https://en.wikipedia.org/wiki/Cetuximab

Here is some information about the EGFr (ErbB's)s:
https://en.wikipedia.org/wiki/Epidermal ... r_receptor

Here is a representative example of a Third Generation EGFr inhibitor I was involved in developing:
https://en.wikipedia.org/wiki/Dacomitinib
https://www.vizimpro.com/

Good Luck

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

mpbser
Posts: 953
Joined: Wed Apr 19, 2017 11:52 am

Re: Calling all those on anti-EGFR therapies

Postby mpbser » Fri Feb 15, 2019 6:28 pm

Wow, thanks for the input. You've given me a lot to chew on. Thanks!
Wife 4/17 Dx age 45
5/17 LAR
Adenocarcinoma
low grade
1st primary T3 N2b M1a
Stage IVA
8/17 Sub-total colectomy
2nd primary 5.5 cm T1 N0
9 of 96 nodes
CEA: < 2.9
MSS
Lynch no; KRAS wild
Immunohistochemsistry Normal
Fall 2017 FOLFOX shrank the 1 met in liver
1/18 Liver left hepatectomy seg 4
5/18 CT clear
12/18 MRI 1 liver met
3/7/19 Resection & HAI
4/1/19 Folfiri & FUDR
5/13/19 HAI pump catheter dislodge, nearly bled to death
6-7 '19 5FU 4 cycles
NED

mpbser
Posts: 953
Joined: Wed Apr 19, 2017 11:52 am

Re: Calling all those on anti-EGFR therapies

Postby mpbser » Fri Feb 15, 2019 7:08 pm

Interesting article on the subject:
https://esmoopen.bmj.com/content/3/4/e000353

"Overall, all current guidelines conclude that patients with RAS wt mCRC who do not receive a biologic in the first line (but are fit enough to receive it in later lines) should be considered candidates for an anti-EGFR therapy in the next available line."

I don't know if my husband would be considered fit enough. Another question to ask Dr. Kemeny.
Wife 4/17 Dx age 45
5/17 LAR
Adenocarcinoma
low grade
1st primary T3 N2b M1a
Stage IVA
8/17 Sub-total colectomy
2nd primary 5.5 cm T1 N0
9 of 96 nodes
CEA: < 2.9
MSS
Lynch no; KRAS wild
Immunohistochemsistry Normal
Fall 2017 FOLFOX shrank the 1 met in liver
1/18 Liver left hepatectomy seg 4
5/18 CT clear
12/18 MRI 1 liver met
3/7/19 Resection & HAI
4/1/19 Folfiri & FUDR
5/13/19 HAI pump catheter dislodge, nearly bled to death
6-7 '19 5FU 4 cycles
NED


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