Are you currently (or have you been) in a Clinical Trial?
Comments
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Cure-ious,
I just started cycle 11 (4 week cycle) I'm now getting it with nab-paclitaxol, started with paclitaxol, had 4 infusions of that with serious reactions. It will be interesting to see what they decide is best to give with it. I'm on 1/2 dose due to rash from tomi. MO had to put me on 2mg dexamethasone due to SOB. It has been so helpful, I have my life back again. I just worked out in the garden for 3 hours this afternoon. Prior to this I wouldn't have been able to work for 30 mins without taking many breaks. Other than my foot neuropathy getting kind of bad, it hasn't been too bad at all. thanks for all the research that you do Cure, I really appreciate all the info you share & I forget to tell you that.
cheers, dee
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Dee,
So happy to hear your SOB is better.
I had a terrible rash after getting off of Piqray. I saw a Dermato Oncologist at Stanford who told me to take Zyrtec (OTC antihistamine) twice a day and put a thin coating of Triamcinolone cream on the rash. It went away within hours. I had been suffering for two weeks before that sitting around with ice packs all over my body.
Hope you will be able to find relief.
Hugs, Susan
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Susan, I was just reading on CAR cells for Her2-expressing cancers, using macrophages rather than T cells. In mice these cells look good and FDA fast-tracked the approach last year.
In the first 3 patients it appears to be safe, and they can see changes in microenvironment, in a subsequent group they will label the CAR-Ms to monitor their tracking and follow how they infiltrate tumors. Obviously its in very early days, but at least this approach is in clinical trial.
https://www.onclive.com/view/dr-reiss-binder-on-in...
https://www.onclive.com/view/car-macrophage-ct-050...
https://www.onclive.com/view/fda-grants-fast-track...
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Susan and GG27 this is amazing! I am so happy that both have had fantastic results and improved QOL with the ability for Susan to walk up hills (in SF!) and GG to be able to garden for hours. Thank you both for doing these trials. Both give me great hope for good treatments to come!
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I was reading this article about the "Promising Clinical Benefit" of Enhertu (https://www.cancernetwork.com/view/trastuzumab-deruxtecan-yields-promising-clinical-benefit-in-her2-positive-metastatic-breast-cancer). What surprised me was this line, that Enhertu "yielded favorable activity in the overall population, meaningful benefit in heterogeneous patients, and even a reduction or loss of HER2 expression." Why would it be a good thing to lose HER2 expression? Wouldn't it mean that you would be excluded from a number of very effective treatments? If this is true, I would not take Enhertu. I have never heard that Enhertu has this effect.
Cure-ious, Great news about the fast-tracking of CAR-M! So many new treatments in the pipeline my head is spinning trying to keep track of them!
Hugs, Susan
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Well, Susan, HER2 expression is what is driving the cell growth, so if you lose/reduce expression the growth is reduced, which is a good thing and you can stay on the drug longer. When the cancer finds a way around the drug the Her2 expression also comes back, in most cases- for all progression there has been some change in the cancer so they have to check the genomics of the cancer, but most likely it stays with Her2 because that is such a robust pathway for these cells to grow.
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Thanks for the explanation, Cure-ioius. I know next to nothing about HER2 since it has never before been relevant to me until recently. So with these ADCs like Enhertu and ARX-788, they target the HER2 pathway but this is different from the amount of HER2 expression. As these cells are destroyed by the toxic payload, your HER2 expression is going to be reduced? I know there are differences between HER2 mutation, amplification and protein overexpression but it is confusing since they seem to be used interchangeably.
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With the ADCs, once the HER2-expressing cells die, the chemo leaks around locally, killing other tumor cells whether or not they have HER2, so I guess you are losing mostly HER2+ cells but also some non-HER2 expressing cells- you never get them all tho! We want to reduce the level so much the immune system can keep the rest of the cancer in check, and maybe CAR-T + immunotherapy can get that.
For HER2-positive cancer, the region of the genome where the HER2 gene resides gets amplified/copied over and over so the cells can get 25-50 copies of the gene (rather than the two normal cells have), so of course they end up making lots more HER2 protein, which is easily visible by staining. Interestingly, the CDK12 gene resides close to HER2 gene in the genome (turns out, it is a neighbor!) so many of these cancers also make high levels of CDK12, and may be sensitive to the CDK12 inhibitors that are in production.
HER2 drives a growth pathway different from the estrogen receptor pathway. So when ER-positive cancer mutates to get around a drug, it sometimes mutates in a way that allows the cells to grow on HER2 pathway. This can happen by turning on pathways that up-regulate HER2 protein expression, or by mutating the HER2 gene, in which case the level of HER2 protein is the same as normal cells, but the HER2 kinase activity is much more active and so its just hyper-active, stronger than the normal protein.
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Thanks, Cure-ious! Great information. This stuff is so interesting. Sometimes I wish I could go back to school and study medicine. I majored in Electrical Engineering but ended up having a career managing hedge funds. I thought that my career was fun and complex but medical research is so much more complex with new discoveries constantly changing the landscape. I can tell from your messages that you love what you do.
Hugs, Susan
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Dear Susan, thanks a lot for more info on ARX788. I have been following its development for several years already and you are the first I know who gets it. Initial data showed it was somewhere "between" T-DM1 and T-DXd with its ORR, PFS, etc., but it really can have its own place among ADCs in the future as it has a different payload. It would be amazing to see its phase3 clinical trial in comparison with other monos and combos. As I mentioned before, if you are HER2++, and although you have already been on Trodelvy (similar but... ehh, a bit different payload), you still have another super gun - T-DXd! Anyway, I believe you will not need it, and will continue to improve, and today we celebrate with you!
Saulius
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Susan... are you HER2+ or HER2-??
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Thanks, Saulius. I didn't know that ARX-788 had a similar payload to Trodelvy. ARX788 delivers two toxic payloads, the tubulin inhibitor AS269 and MMAF, a synthetic auristatin derivative that inhibits cellular proliferation by disrupting tubulin polymerization. In what ways are these similar to the topoisomerase I inhibitors in Trodelvy and Enhertu?
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SuperBowl Ads are always interesting, but I thought this one featuring Mary J Blige was powerful:
Mary J. Blige Makes Time for Preventative Health in Hologic's Super Bowl 56 Ad:
https://www.adweek.com/brand-marketing/mary-j-blig...0 -
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Nicole,
I am HER2 2+, so equivocal.
Hugs, Susan
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So ya'll I just talked to a woman on FB Barbara Bigalow....she is 6 years in remission yes...remission from Keytruda and Eribulin...while it almost killed her...literally she had a massive inflammatory response and had to be put into a coma for a week...it also cured her she has been on NO treatement for 6 years.....she was a receptor flipper as well...from HER2- to TNBC.... Cross posting....
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Hi Cure-ious. Following up on the earlier conversation about the HER2 pathway and endocrine resistance, it looks like the Vancouver Cancer Agency is participating in the Destiny 6 trial (https://clinicaltrials.gov/ct2/show/NCT04494425). I'll mention it to my MO tomorrow. Of course, first thing is to get him to consider a biopsy...
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Nicole,
She is one of the two people who were successful in these types of treatments, along with Judy Perkins. Barbara has a blog that tells her whole story, and there are loads of articles about her on the internet. She does some speaking, like Judy Perkins.
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oh ok...thats why her name sounded familar...
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Yeah, but I don't think she was treated at NIH -- I think she was treated at Dana Farber. What almost killed her was a cytokine storm, but I went to a seminar two years ago where the researchers were saying that they have much more of a handle on things with respect to that at this point in time.
Look at the liver thread -- Moth posted an article from NIH.
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here is what she said on FB
After three months, I began to fail drastically. I was hospitalized with hyper-inflammatory syndrome and complete organ failure. In a last-ditch effort to save me, I was placed in a medically induced coma for days and given a less than 10% chance of surviving. Steroids, at a massive dose, were administered, as well as hemodialysis. Miraculously it worked. After a month in the hospital and a 42-pound weight loss, I was transferred to an acute rehab facility so I could re-learn how to walk, swallow, sit up, use my hands, etc. I managed to get off hemodialysis too. Seven weeks later, I went home with months of Physical Therapy to follow. Currently, I am treatment free and have been for over five years—the unicorn!
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SadieS- Well, because the Destiny06 trial comparison is to physician-choice chemo, and because of that they prohibit having any prior chemo in the metastatic setting. These trial requirements are just obnoxious, so many criteria, its similarly hard for bone-only mets people to find anything available to them.
A biopsy and genomic analysis like Foundation One or Tempus could steer you in a good direction, to be sure these tests can come up with no-actionable insights but it makes no sense to not even try. Is there someone else there you could consult with?
PS Here is an interesting trial of a new (TTK) kinase inhibitor: https://clinicaltrials.gov/ct2/show/NCT02792465
Something to watch to see if they are getting good results- and for sure before then you'd want to have Enhertu or Trodelvy ADCs and/or immunotherapy combo and/or PARP inhibitor, you just need to get the genomics/proteomics information about the cancer to see what is indicated.
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Well that sucks! Thanks for the explanation and suggestions. His issue with genomic testing is that, in the past, they pointed to treatments he would try regardless but that conversation was five years ago and the landscape has changed. I did learn today that Piqray is not approved here despite the fact that there was a trial in BC (Dee was on it I think) but my extended health plan covers it with approval. Hopefully Eribulin is beating things back so I have some time but, like Susan, I’m trying to think ahead. Appreciate your wisdom!
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Sadiesservant,
I was on the Piqray trial, I'm surprised it's not being covered. I know what you mean about thinking ahead. I'm a bit worried that I might be getting close to progression on the trial I'm on right now. I didn't ask what the next step was as I still have at least 4 weeks to wait for a CT and results. But I get antsy not knowing what the plan is. Fingers crossed that Eribulin works for you. cheers, dee
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Dear Susan, no, I wanted to say that T-DXd and Trodelvy had similar payloads - in ARX case it is not similar at all... Sorry, sometimes perhaps I do not express myself in English well enough, ehhh:)
For those who want to know more on what dr. S. Rosenberg does, I paste a link to his lecture.
I think the other patient that was cured along with J. Perkins was not a BC patient. A. Bigelow was not part of these trials. He tells all of this this in his presentation. This is the link that was already here, so nothing new BUT A MUST WATCH!:)
Saulius
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Saulius,
It was my bad. I misread your post. Thanks again for your valuable input.
Hugs, Susan
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Saulius,
Thank you so much for sending us the link to the talk by Dr. Steven Rosenberg. As a nonscientist, I found some of the presentation to be difficult to follow, but nevertheless, it was fascinating to hear about the process of metastasis and theories about how to cure cancer metastasis.
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Barbara Bigelow was cured at Dana Farber, after going into sepsis as a result of a infected port that happened while she was getting chemo-immunotherapy- terrible way to get cured
Judy Perkins was cured from the Rosenberg CAR-T/TIL trial at NIH in 2018, and this recent followup from the NIH states that two other women have now also been (apparently) cured, and like Perkins no longer take any treatment for their cancer:
"The other two women had tumor shrinkage of 52% and 69% after six months and 10 months, respectively. However, some disease returned and was surgically removed. Those women now have no evidence of cancer approximately five years and 3.5 years, respectively, after their TIL treatment."
https://www.nih.gov/news-events/news-releases/nih-...
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Saulius,
Thanks for sharing Dr. Rosenberg's lecture. It gave me a lot of hope. Unfortunately, his answer to the last question about brain mets was that it didn't work well for brain mets so patients with brain mets are excluded from the trial. I suspect it will be the same with the CAR-M trial.
- Susan
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Dear Susan, yes, lymphocytes (and that is also TILs) are not very good in crossing BBB but scientists are working to make that happen. Also it is interesting that WBCs manage somehow to modify BBB in multiple sclerosis (MS) case, so there are mechanisms how they can go there, and future TILs will probably work with brain mets too. Saulius
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