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PD-L1 Therapy for Metastatic Triple Negative

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Forum Name: TNBC Metastasis/Recurrence Users
Forum Description: A place to discuss metastatic disease
URL: http://forum.tnbcfoundation.org/forum_posts.asp?TID=13123
Printed Date: Mar 28 2024 at 3:25am
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Topic: PD-L1 Therapy for Metastatic Triple Negative
Posted By: pj123
Subject: PD-L1 Therapy for Metastatic Triple Negative
Date Posted: Apr 29 2017 at 1:39pm
Follow up on http://forum.tnbcfoundation.org/topic13067_post130990.html" rel="nofollow - http://forum.tnbcfoundation.org/topic13067_post130990.html

Recently the doctor suggested to get a test for PD-L1 expression for my aunt. I wanted to ask if anyone has undergone this therapy for Metastatic Triple negative breast cancer. If yes it would be valuable if they can share their experience. 

Another question was there are many different tests of PD-L1 for various cancer, I think for breast cancer "PD-L1, IHC with Interpretation" ( http://www.questdiagnostics.com/testcenter/TestDetail.action?ntc=94007" rel="nofollow - http://www.questdiagnostics.com/testcenter/TestDetail.action?ntc=94007 ) is the one that should be done, am I right ? Also, if test shows that the therapy is applicable then the doctor suggested that "Avelumab" drug will be used which I guess the doctor will tell us how and where to get it from.

Thank You.



Replies:
Posted By: gordon15
Date Posted: Apr 30 2017 at 10:28am
Has she had any molecular genetic testing of the tissue? My wife's doctor sent out to FoundationOne lab, they found "EGFR" (F795C) gene mutation and recommended "Lapatinib" (FDA approved in her cancer type) should she have recurrence. They even listed the approved therapy drugs "in other cancer types" Of course, we have no idea what will work in the future, but this is latest research (Moores Cancer Cntr)

Also sent to Carris.,
 sorry... I don't see anything about PD-LI in her results. She is 66 yrs old, your aunt is younger, perhaps inquire?


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wife: IDC/Lobular Stage2B 2008 lumpectomy/TAC+rads
TNBC Stage 3A/w/metaplastic/squamous Nov2015 Carboplatin-Gemzar chemo/masectomy Taxolchemo+rads 4-16
PET scan stable 9-2016/ 1-2017


Posted By: pj123
Date Posted: Apr 30 2017 at 11:06am
Thank you for the reply. 

No molecular genetic testing has been done so far in her case. Yes, she is younger (52 years old). When you said "perhaps inquire" did you mean inquire with the doctor to get her genetic testing done or something else ?

Thank You


Posted By: gordon15
Date Posted: Apr 30 2017 at 11:16am
yes, inquire with the doctor .


-------------
wife: IDC/Lobular Stage2B 2008 lumpectomy/TAC+rads
TNBC Stage 3A/w/metaplastic/squamous Nov2015 Carboplatin-Gemzar chemo/masectomy Taxolchemo+rads 4-16
PET scan stable 9-2016/ 1-2017


Posted By: 123Donna
Date Posted: May 01 2017 at 8:09am
http://www.ascopost.com/issues/january-25-2016/immunotherapy-for-breast-cancer-early-lackluster-study-results-yet-promise-remains/" rel="nofollow - http://www.ascopost.com/issues/january-25-2016/immunotherapy-for-breast-cancer-early-lackluster-study-results-yet-promise-remains/

http://forum.tnbcfoundation.org/immune-therapy-to-fight-cancer_topic9649_post128658.html?KW=Keytruda#128658" rel="nofollow - http://forum.tnbcfoundation.org/immune-therapy-to-fight-cancer_topic9649_post128658.html?KW=Keytruda#128658

Here's a link to a member that was on Keytruda, an anti PD-L1 therapy.  It worked for a while, but then progressed and she had to consider other treatment options.

http://forum.tnbcfoundation.org/ct-scan-this-morning_topic9532_page14.html" rel="nofollow - http://forum.tnbcfoundation.org/ct-scan-this-morning_topic9532_page14.html


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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: pj123
Date Posted: May 01 2017 at 9:37am
Thank you for all the information. It is certainly helpful.


Posted By: 123Donna
Date Posted: Jun 05 2017 at 9:49pm

Keytruda Shows Meaningful Clinical Benefit When Combined with Standard Therapy 


http://breastcancer-news.com/2017/06/01/keytruda-improves-aggressive-breast-cancer-response-to-standard-therapy" rel="nofollow - http://breastcancer-news.com/2017/06/01/keytruda-improves-aggressive-breast-cancer-response-to-standard-therapy


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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Jun 09 2017 at 11:29am

Cancer Drug Proves to Be Effective Against Multiple Tumors

http://www.nytimes.com/2017/06/08/health/cancer-drug-keytruda-tumors.html" rel="nofollow - http://www.nytimes.com/2017/06/08/health/cancer-drug-keytruda-tumors.html


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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Jun 09 2017 at 7:17pm
http://www.yahoo.com/beauty/new-cancer-drug-effective-tumors-fda-approved-immediately-164122959.html" rel="nofollow - http://www.yahoo.com/beauty/new-cancer-drug-effective-tumors-fda-approved-immediately-164122959.html




-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: pj123
Date Posted: Jun 09 2017 at 10:52pm
Thanks 123Donna, I believe this drug is effective on patients with PD-L1 positive. However, my aunt was tested for PD-L1 and the result was negative. 


Posted By: 123Donna
Date Posted: Jun 10 2017 at 12:08pm
pj123,

You are correct.  It's most promising in patients who's tumors tests positive for the PD-1 mutation.  I'm sorry your aunt couldn't benefit from this drug.

"The patients all carried genetic mutations that kept their cells from fixing damaged DNA. Pembrolizumab (Keytruda) is known as a PD-1 blocker,  http://blog.dana-farber.org/insight/2015/05/the-science-of-pd-1-and-immunotherapy/" rel="nofollow - an emerging type of  http://blog.dana-farber.org/insight/2015/05/the-science-of-pd-1-and-immunotherapy/" rel="nofollow - immunotherapy drug  that helps the immune system find cancer cells and attack tumors."


-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: Manchubby
Date Posted: Jun 15 2017 at 5:23pm
Dear PJ123,

I share your disappointment that your aunt tested negative for the PD-L1 mutation with respect to Keytruda's effectiveness. To add to yours and Donna's observations one not only has to test positive for PD-L1 but it also has to have a strong expression. My wife tested positive for PD-L1 but it was weak and her trial with Keytruda was subsequently stopped after 3 cycles due to disease progression. Sorry if this does not sound very positive but I thought I'd share this for what its worth. 

I wish your aunt the best in her treatment.

Best regards,

Manc_hubby


Posted By: 123Donna
Date Posted: Jun 16 2017 at 9:47am

Data from I-SPY 2 TRIAL shows potential of a new precision medicine drug therapy for breast cancer patients


http://www.uab.edu/medicine/news/latest/item/1558-data-from-i-spy-2-trial-shows-potential-of-a-new-precision-medicine-drug-therapy-for-breast-cancer-patients" rel="nofollow - http://www.uab.edu/medicine/news/latest/item/1558-data-from-i-spy-2-trial-shows-potential-of-a-new-precision-medicine-drug-therapy-for-breast-cancer-patients


-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: gordon15
Date Posted: Jun 16 2017 at 6:04pm
Thanks for you comments. My wife has a genetic mutation "EGFR" with the doctors recommending (1) FDA approved drug, should she have a recurrence.

Her latest blood-marker tests from Guardant lab show positive for BRCA2 which wasn't their before. Don't know what to make of this.


-------------
wife: IDC/Lobular Stage2B 2008 lumpectomy/TAC+rads
TNBC Stage 3A/w/metaplastic/squamous Nov2015 Carboplatin-Gemzar chemo/masectomy Taxolchemo+rads 4-16
PET scan stable 9-2016/ 1-2017


Posted By: 123Donna
Date Posted: Feb 21 2018 at 6:38pm

Newly Identified Potential Therapeutic Approach Kills Triple-Negative Breast Cancer Cells in Pre-Clinical Study

Findings suggests potential new area of focus for checkpoint blockade immunotherapy


Triple-negative breast cancer (TNBC), a highly aggressive, relapse-prone cancer that accounts for one-fourth of all breast cancers, could be the focus of a new area of study for immune checkpoint blockade therapy.  A team of researchers at The University of Texas MD Anderson Cancer Center revealed that in TNBC a cell process called glycosylation is required for PD-L1/PD1 molecules to interact and identified exactly how and why glycosylation is so crucial. Findings from the study were published in the Feb. 12 issue of  http://www.cell.com/cancer-cell/home" rel="nofollow - Cancer Cell .

Immune checkpoint blockade therapy relies on connections between PD-L1 and its sister molecule, PD1, found on T-cell surfaces, allowing cancer cells to go undetected by the immune system. Blocking PD-L1 and PD-1 interaction has been the basis for successful immunotherapies already in use in other cancers.

“Glycosylation is a process that attaches portions of sugar molecules called moieties to the protein providing it fuel to grow and spread,” said  https://faculty.mdanderson.org/profiles/mien-chie_hung.html" rel="nofollow - Mien-Chie Hung, Ph.D. , chair of  https://www.mdanderson.org/research/departments-labs-institutes/departments-divisions/molecular-and-cellular-oncology.html" rel="nofollow - Molecular and Cellular Oncology . “Glycosylation of PD-L1 in tumor cells stabilizes PD-L1, but it is largely unknown whether sugar moiety by itself is required for binding to PD-1 to suppress anti-tumor immunity.”

Hung’s research group shed further light in this area through discovery of glycosylated PD-L1 (gPD-L1), and worked with STCube Pharmaceuticals, Inc. to develop anti-gPD-L1 antibodies that recognize this glycosylated form of PD-L1, killing tumor cells while not harming healthy ones.

To improve the therapeutic efficacy of anti-gPD-l1 antibody, the team linked a potent small molecule chemotherapy agent, called MMAE, to the anti-gPD-L1, creating a new antibody drug conjugate (ADC), called anti-gPD-L1-MMAE, which resulted in higher therapeutic efficacy in animal models. Hung believes the development of this glycosylated PD-L1 ADC (anti-gPD-L1-MMAE) may represent a new generation of immunotherapy that is more targeted with fewer adverse effects.

“We demonstrated that gPD-L1 is an excellent candidate for ADC as sugar moiety is critical for PD-L1’s detrimental role in TNBC,” said Hung. “Immune checkpoint blockade treatment options remains limited in TNBC, so identifying new immune checkpoint targets to improve upon current therapy is urgently needed.”

https://newswise.com/articles/newly-identified-potential-therapeutic-approach-kills-triple-negative-breast-cancer-cells-in-pre-clinical-study" rel="nofollow - https://newswise.com/articles/newly-identified-potential-therapeutic-approach-kills-triple-negative-breast-cancer-cells-in-pre-clinical-study



-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15




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