Reconstruction surgery while taking this new drug, Nerlynx?

carmstr835

I am scheduled for reconstruction DIEP on July 10 and just completed my 17 cycles of herceptin and perjeta. I am wondering about healing and scar formation with this new drug. My PS would not do my reconstruction until 6 weeks after Perjeta because of a new study published this past December inhibiting healing while on Perjeta. I was wondering if Nerlynx works the same way as Perjeta and if so, what about us that are planning reconstruction? I haven't discussed this with my PS surgeon yet, and thinking about waiting until after my surgery to begin the Nerlynx, but then I want all the value I can get from this new drug since I am not taking the hormone blockers. Maybe I should delay my reconstruction another year?

Lula73

Perjeta and Nerlynx work in different ways. They are both used to treat HER2+ breast cancer and work on the same types of cells, however they do it very differently. Nerlynx is a kinase inhibitor that binds to receptors on certain types of cells not allowing them to function as they would without the drug. Perjeta is a monoclonal antibody that inhibits specific signaling pathways, blocks a certain type of heterodinerization and mediates antibody dependent cell mediated cytotoxicity. See the references for each below:

Nerlynx: 12.1 Mechanism of Action

Neratinib is a kinase inhibitor that irreversibly binds to Epidermal Growth Factor Receptor (EGFR), Human Epidermal Growth Factor Receptor 2 (HER2), and HER4. In vitro, neratinib reduces EGFR and HER2 autophosphorylation, downstream MAPK and AKT signaling pathways, and showed antitumor activity in EGFR and/or HER2 expressing carcinoma cell lines. Neratinib human metabolites M3, M6, M7 and M11 inhibited the activity of EGFR, HER2 and HER4 in vitro. In vivo, oral administration of neratinib inhibited tumor growth in mouse xenograft models with tumor cell lines expressing HER2 and EGFR.

Perjeta: 12.1 Mechanism of Action

Pertuzumab targets the extracellular dimerization domain (Subdomain II) of the human epidermal growth factor receptor 2 protein (HER2) and, thereby, blocks ligand-dependent heterodimerization of HER2 with other HER family members, including EGFR, HER3 and HER4. As a result, pertuzumab inhibits ligand-initiated intracellular signaling through two major signal pathways, mitogen-activated protein (MAP) kinase and phosphoinositide 3-kinase (PI3K). Inhibition of these signaling pathways can result in cell growth arrest and apoptosis, respectively. In addition, pertuzumab mediates antibody-dependent cell-mediated cytotoxicity (ADCC).

Because they work differently you can expect that SEs like poor wound healing or no effect on wound healing will likely be different between the two drugs. Hope this helps!!

carmstr835

Neratinib is a kinase inhibitor that irreversibly binds to Epidermal Growth Factor Receptor (EGFR)

Wound healing and fibrosis[edit]

EGFR has been shown to play a critical role in TGF-beta1 dependent fibroblast to myofibroblast differentiation^[23][24]. Aberrant persistence of myofibroblasts within tissues can lead to progressive tissue fibrosis, impairing tissue or organ function (e.g. skin hypertrophic or keloid scars, liver cirrhosis, myocardial fibrosis, chronic kidney disease).

Thanks, Lula. I appreciate your help and posting this info, but I am still a bit concerned on the ability of this drug to inhibit healing. If this binds to the EGFR and limits its ability to replicate itself, it seems it might inhibit healing. I did read where it does cause acne and skin issues in some people. I am prepared to wait if my PS insists and he is rather skittish when there might be something to impede healing. I was hoping to read where someone was taking it and underwent successful surgery or had a reason to heal a skin issue.

NotVeryBrave

I think that the recommendation is to start Nerlynx within a year of completing Herceptin. You should be able to have your surgery and start the Nerlynx after giving your body a chance to heal. Have you asked your MO about the timing?

carmstr835

Yes, "Not Very Brave", I did mention my concerns with the nurse practitioner and she as going to share my thoughts with my MO. I should have an idea of their suggestions on Jun27th when I go back for cancer marker levels and scans. Just wondering what others have done.

NotVeryBrave

Curious - what cancer markers and scans do you get and how often?

carmstr835

NotVery Brave,

I get CT scans every 3 months because I have 10 lesions on my liver however, only 1 as big as 1 cm; and a 2.6cm lesion on my adrenal gland; and 2 lesions on my lung that were not there before.

My first scan was in May 2017 and when they found the liver lesions. They were rescanned in August after my chemo was completed and they assumed no change means not cancer, there was no change, but they found the 2.6 cm lesion on the adrenal and ordered a MRI that result was, it was likely adipose tissue. The Lung lesions were not found until November when I had chest pain and breathing issues.

I have had rescans in Jan and March and will again in June.

They have been following them and I got a PET scan in November. It was negative, but PET scans may not be valid for small lesions and mine were only 9mm. They are more concerned about the lung lesions mostly because the inflammation from the radiation has obscured the ability for them to see the lesions to know if they are growing or not sinse November. I think they will decide whether to continue the CT scans depending on what they see this time.

I have been doing 9 day fasting every 3 weeks for the past year and I believe it is stopping them from growing if they really are cancer, but I really don't know if it is or not.

Cancer markers are slowly increasing but not high enough to be concerned about them, the last ct scan showed no change in the adrenal or the liver lesions.

They think it is possible the liver are most likely cysts I have had all my life; the adrenal lesion is generally thought as adipose tissue and the lung could be caused by the radiation treatments. The inflammation will eventually turn to scar tissue and I will likely lose some lung function, but no way to really know what it is in my upper right lung if they can't see it past the inflammation or scar tissue.. I don't want a biopsy.

Cancer marker blood tests:

CA 15-3 (Breast Antigen)

CA 27.29

CEA

NotVeryBrave

Wow - that's a lot of things to be watching! It's hopeful that they don't feel that they are cancerous, but I know that I'd be going crazy with wondering myself. I hope that everything continues to show nothing new!

Hang in there ...