Are you currently (or have you been) in a Clinical Trial?
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Susan, I’m sorry that, after jumping through so many hoops, the outcome was so crappy. These trials seem so difficult to navigate that I’m in awe that you have been able to access so many.
I’m in a place that I really hope something materializes here soon. Got the news today that Xeloda is no longer working. TMs plateaued and liver lesions showing mixed results - some slightly improved and others worse. So, now I wait to talk to my MO to determine where we go next now that I am likely endocrine resistant. Chemos have largely been unsuccessful given my slow moving disease. Getting nervous…..
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Sadieservant,
Are you Her2 low by any chance? It is fairly common to be Her 2 1+ or 2+ and then you could try Enhertu (TDxd). I will be starting it in about 10 days and I also have "indolent" cancer that is progressing again. It is more targeted and I am hopeful- The studies haven't been teased out much for subgroups so far and there aren't huge numbers- but a "waterfall" curve for the efficacy. It is IV. there is a a one hour interview (for general oncologists, but, still quite understandable) with Dr Shanu Modi the primary author of the paper from MSK you could listen to on Breast Cancer Update podcast with Dr Neil Love (available for free wherever you get your podcasts )
I know you are Canadian and I have no idea if covered there- it is quite a break through and as Susan showed there are many ADCs in the pipeline -so more to come
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Hi nkb. Unfortunately my last biopsy came back HER2- again. I was hopeful but no cigar…
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Bummer
Luckily there will be lots of other targets that the monoclonal antibody can go after In the future if you can hang in there. they say the Her2 is the current "docking protein" being used.
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Not planning on giving up. Just regrouping. 😁.
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Good!
Did you do Verzenio as a mono therapy?
Trodelvy? I know it is approved for TN, but, many ER+ have tried it also.
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Sadiesservant - I'm sorry to hear Xeloda is no longer working for you. I also have slow growing ER+ tumours but even so have usually managed a 6 month or so response to various chemos. It adds up. It's a shame the lowHER2+ option isn't available to you. My latest biopsy is now being tested, so I'll find out it that will be something I can try in the future.
I just bounced out of an ADC trial (enfortumab vedotin, used for urothethial cancers now being tested in other cancers, target Nectin4 protein) - but I did get 6 months out of it. Side effects were there so I had 2 dose reductions. Anyhow, it's listed as being offered in Vancouver. https://clinicaltrials.gov/ct2/show/NCT04225117 Hopefully your oncologist has other alternatives too.
I'm now waiting to hear about another trial that just got slots in Ottawa. I don't know it's NCT yet, but will share if it's in Vancouver too.
SusaninSF - I'm sorry to hear about the further twist in accessing the new trial. Just crummy.
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Back from Spain, great trip, but its too hot here at home!
So, there is a new lisiting for a clinical trial for the ARV-471 Estrogen Receptor Degrader (PROTAC), which will be tested here in combination with Everolimus. It's Phase One, only 32 patients, a quick check that finishes up next year and they follow patients a further year. Only a handful of sites. Requires prior CDK4,6 inhibitor and endocrine therapy, allows only one prior chemo, requires measurable or non-measurable (evaluable) disease per RECIST (not sure, does that mean it does allow bone-only mets?)
Anyway, for people looking for more endocrine therapy after progression on Ibrance with Femara and/or Faslodex, this could be a good option:
https://clinicaltrials.gov/ct2/show/NCT05501769
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Sadiesservant- on the thread about new research someone just posted the results of the Tropics02 study of Trodelvy in ER+ Her2 negative disease. sounds really exciting. if link doesn't work it works on the new research thread. super exciting!
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Thanks! I’ll look into it. I’m trying for ARV-471 and it’s interesting they are pairing with Everolimus which I have not been exposed to yet. However, even if there was a site close by, I would be excluded based on the number of chemotherapy regimens I have been on. 😔
I did double check my recent biopsy and unfortunately the HER2 measure was zero so all HER2 low treatments are off the table, at least for now. Not sure when I will speak to my MO. I suspect he’s doing his homework…
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I just had a second opinion consult with Mayo Clinic Rochester after I progressed on Ibrance and Letrozol. Good visit; well worth it. The MO encouraged me to consider the Prembrolizumab (monoclonal antibody) + Fulvestrant study at UW Madison - sometimes referred to as the Big 10 Study. On ClinicalTrials.gov number is: BTCRC - BRE 16-042. It's open to Her2 low patients. However after talking with the study coordinator, I learned I would have to repeat my liver biopsy (just had it done 8/15/22), and repeat CT scans of abd and chest (just had scans done 8/01/22), and could not start fulvestrant prior to the study as planned because it would be considered third-line treatment. These seem like doors closing to me. The Pembro is given by infusion every 3 weeks and the possible side effects cover over four (4) pages. This just seems so overwhelming to me. The Mayo MO also mentioned a study they're doing Destiny 06, which I will look into.
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Thanks, Wendy and Nanci!
PY-314 is "a humanized monoclonal antibody (mAb) that specifically binds Triggering receptor expressed on myeloid cells 2 (TREM2) and is designed to deplete TREM2-expressing tumor associated macrophages (TAMs) through antibody dependent cell mediated cytotoxicity (ADCC) and/or antibody dependent cell mediated phagocytosis (ADCP). "
Description from the company's website. Basically, it's a kind of immunotherapy that is trying to deplete macrophages protecting the tumor. Does that sound right, Cure-ious?
Hugs, Susan
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Susaninsf,
You wrote: "I had such a bad reaction to Keytruda". What reaction did you have to Keytruda? Did your side effects resolve? I'm considering entry into a study of Keytruda (IV infusion every 3 weeks) plus Fulvestrant. Referred to as the Big Ten Study - it's investigational. This would be my first clinical study and I'm extremely nervous. If I don't do the study then my MO would start me on Everolimus plus Fulvestrant. I was on Ibrance plus Letrozole until progression.
Wendy
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Wendy,
I was on Abraxane and started to see progression so I asked if I could add in Keytruda. A Hail Mary, really, since it was only approved for TNBC. My MO said, ok. I figured, if it didn't work, I could just get off of it. Not only did it not work but after less than a month on it, I developed some bad mouth sores. Got off of Keytruda but the mouth sores took over the entire inside of my mouth. At one point, I couldn't even drink water without pain. The doctors who looked at it said they'd never seen anything that bad. This lasted for about a year and a half. Finally, took a massive dose of steroids and it healed.
That being said, I think this was a very unusual reaction and not something you should expect. I think the question you should be asking is about the efficacy of Keytruda for ER+/HER2- MBC. I don't think Keytruda has great numbers for MBC in general, results for TNBC, PD-L1 positive disease > 10, were good.
Here's a photo of part of my mouth:
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Susaninsf,
Oh boy.....I would be devastated if I ended up with mouth sores like that. Happy to hear they eventually healed. I see a periodontist every 3 months in an effort to keep 3 dental implants with problem pockets stable and mouth sores like that would just create bigger problems.
The Keytruda plus Fulvestrant study for ER+ Her2 Neg has a total of about 30 patients at all the Big Ten locations, but apparently only one or two patients at UW Madison. To be eligible I would have to repeat the liver biopsy, repeat CT scans, and not start Fulvestrant. I've been off all treatment since Aug 15. If I don't do the Big Ten study then my MO would start me on Everolimus (Afinitor) plus Fulvestrant. Afinitor can cause somatitis too. My genetic study came back showing ESR1 mutation, but no PI3K mutation.
The Mayo doctor I saw for second opinion (video visit) was encouraging of the Big Ten study. Mayo has a Destiny 06 Trial with Enhertu that I'm going to learn more about, but that would involve travel. I feel completely overwhelmed and out of my league in all this.
Thank you for all your support and information.
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cure-ious,
My genetic test showed my tumor has the ESR1 mutation and no PI3K mutation. Not sure what this indicates for other estrogen based therapies? What do you know about FDA approval for Elacestrant?
I'm still mulling over the Big Ten Keytruda plus Fulvestrant trial and have noted your suggestions about adding Celebrex. However to qualify I would need to repeat the liver biopsy (just had one), repeat CT scans, and hold off on starting fulvestrant until I'm in the trial. I'm now on no treatment, but my MO says my labs indicate waiting is OK. The other option offered to me is Everolimus plus Fulvestrant.
I had a second opinion consult with Mayo that went well. The MO was positive and encouraging about the Big Ten study, but Mayo also has the Destiny 6 trial with Enhertu (edited).......I just learned I'm not eligible.....only patients who have failed on two endocrine treatments are eligible. The Mayo MO also said I had some other markers (micro-satellite - low; tumor mutation burden - low) on my genetic tests that indicate I would not be eligible for any immune therapy unless part of a study. As I understand Keytruda it targets PDL1. I think my PDL1 is low, so I question the rationale for me taking Keytruda. Also long term side effects are possible after stopping the drug because Keytruda affects the Immune system.
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Just read details of Destiny04- the study on enhertu for Her2 low- 77% had liver mets, 33% had lung mets, 6% had brain mets. no bone only- once again- studies don't represent a major group of folks with metastatic breast cancer. we will all be jumping on this Med with no data. and no opportunity to try a drug before it is approved.
Starting it on Tuesday- fingers crossed that people with bone only mets get a good response also.
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Excellent point, Nkb, its ridiculous that trials do not accept people with bone-only mets!!! Hopeful that you will get an even better response than the (very good response) they got in the trial...
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Good luck, nkb!
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Thanks Cure-ious and Susan!
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To All,
I've been reading about Lasofoxifene by Sermonix Pharmaceuticals. It's an oral SERM (selective estrogen receptor modulator) that targets the ESR1 gene mutation. If my understanding is correct, up to 40% of breast cancer patients develop this mutation after exposure to AI drugs. I just learned I have that mutation.
There have been two studies using this drug in combination with a CDK4/6 inhibitor for MBC patients: Elaine1 and Elaine2. The Elaine2 Study is still Active and not recruiting.
https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.16_suppl.1022
Lasofoxifene has not received FDA approval for use in MBD, but it was approved several years ago for other purposes (osteoporosis and vaginal atropy) and has a good safety profile.
I'm not sure why FDA approval is dragging. It seems to my limited grasp, that approval for MBC would constitute "Repurposed" use of an already approved drug. Could patient interest pressure be useful to get approval moving?
There's good information (fairly easy to understand) on the Sermonix website.
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Weninwi - very interesting! Thanks for posting. I am not skilled at looking for clinical trials but it looks like University of Chicago has an active study on this drug for MBC. https://www.uchicagomedicine.org/find-a-clinical-t...
This study is sponsored by Sermonix and the lead Dr. is Gini Fleming at Univ. of Chicago.
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aprilgirl1 and All,
The clinical trial looking at Lasofoxifene relative to Fulvestrant at the University of Chicago is NCT03781063 and on the ClinicalTrials.gov website it says the trial is "Active, not recruiting".
But I found this interesting article: https://sermonixpharma.com/sermonix-pharmaceutical...
Sermonix Pharmaceuticas' Phase 2 Lasofoxifene Trial Poster Receives a GRASP Advocate Choice award, Selected for Post-ASCO Patient Advocate Investigator Discussions.
From the article:
"The ASCO poster describes positive findings from the study related to safety and efficacy in women with ER+/HER2- mBC and an ESR1 mutation who had progressed on previous CDK4/6i therapies. Lasofoxifene is the only selective estrogen receptor modulator (SERM) currently being developed exclusively to treat breast cancers with ESR1 mutations."
GRASP = Guiding Researchers and Advocates to Scientific Partnerships (GRASP) launched in 2019 to unite patient advocates, physicians and researchers through meaningful discussions of cancer-related topics
"GRASP was started in 2019 by two women who are living with breast cancer, based on the recognition that facilitating the patient experience and researcher discussion early and often forges powerful collaborations that positively impact the research landscape."Does anyone know anything about GRASP?Wendy0 -
I attended a Zoom meeting hosted by Life Project. The topic was "HER2-low" and the speaker was Dr. Paolo Tarantino who seems to be an expert on HER2-low. He is also an advisor to Daiichi Sankyo, the company that developed Enhertu.
He said a couple of things that really stood out to me.
1) Her2-low may only be relevant as a target, as it is utilized for ADCs. So far, HER2-positive drugs such as Herceptin, Kadcyla, etc. have not shown efficacy for HER2-low cancers. There are on-going trials testing other non-ADC treatments (See HER2-low Trials).
2) HER-2 targeted ADCs may downregulate HER2 receptors so after being on one you may lose your HER2 positivity, low or high. I know this issue was discussed on this thread a while back. This may explain why I didn't respond to Enhertu after being on ARX-788. It also may explain why ARX-788 did not work for very long (5 months). I'm going to try to get a new biopsy to do fresh ISH and FISH tests.
Basically, these two points greatly reduce the treatment options for HER2-low cancer. So bummed.
Hugs, Susan
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Dear SusaninSF, thanks a lot - really important and interesting points. I was wondering if loss of HER2 receptors is observed in HER2 low space only or was it a general observation for HER2 ADCs? Sure loss happens in HER2 high, we all know it but my question is if it is more often in HER2 low?
Saulius
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Had not considered this, but it makes sense that the loss of HER2 expression would be easier in the absence of gene amplification (true HER2-positive), bummer... It would suggest the better strategy is to let it build up during resistance to endocrine or another unrelated therapy, then use it to benefit from Enhertu or CAR-T
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Hi WeninWi,
I haven't had the pleasure to have attended a GRASP session, but some of my friends have. It's a wonderful way to walk through emerging research on metastatic breast cancer - the patients learn from the researchers and the researcher from the patients. They just wrapped up one event, but there are more on the horizon.
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I hope I built up enough to benefit from Enhertu, since I started it a few days ago.
Staying alive til the next breakthrough-what else can we do?
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nkb,
Wishing you the best on Enhertu! I think it will be your first HER2-targeting ADC so you have a high chance of success!
Hugs, Susan
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For second or third-line, ARV-471 (ER degrader) trial with Verzenio is starting up on Halloween... https://clinicaltrials.gov/ct2/show/NCT05548127?te...
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