Are you currently (or have you been) in a Clinical Trial?
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Saulius thank you for your inspirational and uplifting post. I feel so lucky to have remained stable on I/F for this long. It breaks my heart to read Nicole & Bevs posts and indeed so many others who struggle to get a really decent run out of their meds. So yes Saulius & Dee and everyone else we want a cure but right now I am so grateful for being stable and I’m hanging in there with the rest of you hoping that something is discovered soonthat makes this nightmare go away.
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ok Nicole - I’m no expert but from what I see that’s the result of Immunohistochemistry testing - which is IHC. And looks like HER2neu is in fact 0+ so that would not qualify : (
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So, here is an unusual 'virtual' clinical trial- Johns Hopkins are looking for patients with a specific and RARE mutation in the SF3B1 splicing protein. If the patient has that particular mutation, they recommend that immunotherapy be added to the treatment, along with whatever therapy they and their MO decide to do. No travel is involved, they just would like to find people who have this mutation because they think they may be good responders to immunotherapy.
https://www.hopkinsmedicine.org/kimmel_cancer_cent...
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Nicolerod, my 1st liver bx in 2016 was ER+(medium), PR- HER2 IHC 1+.
THEN at 2020 liver progression, my bx was ER+ (strong), PR+ (weak 10%) and HER2- IHC 0%.
Suspect I have heterogenous mets (?).Guess I will find out when I have to bx again in the future.
I was so excited about Enhertu..darn.
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Yea...Sandi we sound the same. I have not had a biopsy in 2 years...but I definitely will need one....
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Reading along. So... HER2 low is defined as HER1+ or 2+ with a negative FISH. What options in treatment does that open up? Also, I am ER- now, so would those options for HER2 low work for me? (I was HER2 equivocal with FISH negative, so HER2 low????)
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candy - from what I'm reading, nothing is FDA approved right now specifically for HER2low but they are testing Enhertu (and maybe some other drugs).
Herceptin alone was trialed earlier but not shown to be beneficial but these newer trials with Enhertu look more promising because it's a different kind of drug - 'antibody drug conjugate' which combines the antibody with chemo that is able to target cancer cells directly.
I would suggest seeing what your doctor has to say and to keep tabs on this for the future.
Let me add - BCO article about HER2 low https://www.breastcancer.org/research-news/some-breast-cancers-may-switch-her2-status-if-they-come-back
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Chico-congratulation for such a long time being stable on first line treatment. That is soo great.
I liked the oligo talk. I had resection of single liver met in 2017 and liver is clean since than. Also my single bone met was radiated and even though two new appeared close to the original one after one and half year, they were irradiated again and radiotherapist wrote oligoprogression in the report. I am big fan of local treatments whenever possible... combined with systemic of course. Wish you all have good day. Maki0 -
Posting an update to the Johns Hopkins "virtual" trial, which is trying to identify MBC patients who have SF3B1 mutations. Apparently they are looking for a specific mutation that is rare, so they are hoping to find enough eligible patients via the internet to test their hypothesis. No travel is involved, if you have the mutation they are tracking they will help your MO get access to immunotherapy to add on to your ongoing treatments.
In checking my Foundation One Report, I realized that actually I have an SF3B1 mutation.
So I went to their site and filled in their survey, which asks for my contact info and a copy of the F1 report.
If this particular SF3B1 mutation is of interest, they will be in touch.
Here is more information they provide about the rationale for this trial:
We and others have shown that creating an SF3B1 mutation in a cell results in new mRNA transcripts, and that these transcripts are actually translated into abnormal proteins. These preliminary data suggest that spliceosome mutations may produce a high number of neoantigens, or new proteins recognizable by the immune system. If true, this carries direct therapeutic consequences. In a landmark Hopkins' study, Le et al. showed that colon cancers with a high mutational burden demonstrated dramatic responses to anti-PD1 therapy. This has led to an understanding that immune therapy is most effective when some kind of mutational burden produces high numbers of neoantigens.
For this reason, we believe patients with tumors that harbor spliceosome mutations may respond to immune therapy, even if their tumor type or genetic analysis otherwise would not suggest this. We have some evidence that this may prove true: In an analysis of five immunotherapy trials that included gene sequencing, we identified 4/251 patients with spliceosome mutations, all of whom demonstrated at least a partial response to anti-PD1 therapy, one showing a durable remission. We also encountered through our molecular tumor board a patient with a long-term response to anti-PD1 therapy, whose tumor harbored a spliceosome mutation and did not display a high mutational burden.0 -
Cure-ious
Did you find that under the section of unknown variants on your foundation 1 report?
Thanks
Julie
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Hi Julie- It was under Genomics Findings, and listed again under genomics findings with no therapeutic or clinical trial options.
It looks like the most common SF3B1 mutation is K700E, but mine is R625L; nevertheless, I checked and both are hotspot mutations that do screw up splicing. Hoping its a golden ticket to immunotherapy.
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I don't even see a page that says "Genomic Findings" on my F1 report???
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Cure-ious - Thanks for the info on the Johns Hopkins "virtual" trial. I will be interested in their response to you. That would be great if you could get immunotherapy added to your current treatment if you qualify. I looked at my Gardant360 blood biopsy results and the SF3B1 mutation was not tested.
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This trial is on supportive care & uses an amazon Echo or Alexa + weekly phone calls - all about supportive care, tips for managing side effects etc. Recruiting now. I read on twitter open to North America. email bkanski@phs.psu.edu for more info
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Moth, yes. We actually posted about that on our boards too, per their request.
Here are the details https://community.breastcancer.org/forum/8/topics/...
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New paper in Nature Comm shows that disabling SIRPa in macrophages causes them to go into overdrive following radiation, and recruit activated T cells to eliminate the cancer, not only locally at the sites of radiation but throughout the body (the abscopal effect) in mice. They needed to both get rid of SIRPa in macrophages and radiate, either treatment on its own was not sufficient to clear out the cancer body-wide. Not clear how this would translate to therapy in humans, but they say it should work on any cancer type and hope to start clinical trials next year.
https://www.nature.com/articles/s41467-021-23442-z
https://medicalxpress.com/news/2021-05-immunothera...
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I know of a friends husband who had an abscopal effect after radiation for stage IV kidney cancer, The radiation was the only treatment he had received and all tumors in his body regressed and disappeared. His doctors said the radiation sparked an immune reaction that enabled his own system to combat the cancer. Truly amazing! Now he is a thankful and happyresearch subject.
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From the ASCO2021 abstracts, a failed trial:
VERONICA phase 2 trial for 2nd/3rd line MBC
Venetoclax (a Bcl-2 inhibitor) with Fulvestrant PFS was 2.7 mos compared to Fulvestrant alone- PFS 1.9 months for Fulvestrant alone
There were some hopes for this, but anyway its good to know about failed trials, and a reminder how ineffective fulvestrant is on its own...
PS Right after this comes BestBird's abstract, advocating for dosage assessments and better MBC QOL- Go Anne, you rock!!!
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WeareOne: Any more news as to when the ARV-471 trial may open at Stanford? And any update about the NCT03970382 trial? Thanks!!
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Cureious did you get in the Hopkins trial with that special mutation you have?
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Hi Nicole!
I have not yet heard back from Johns Hopkins. But in the meantime, I have been reading about the SF3B1 mutation. It leads to screwed up mRNA splicing, and can result in the production of neoantigens (proteins different than normal cell proteins) being made in the cancer and some will end up getting shoved on the surface of the cancer and attract the immune system. The normal way we think of neoantigens getting made is by having lots of DNA mutations due to mutations in DNA repair proteins (BRCA1, and many others). My tumor mutation burden is 1, so my cancer is not like that and normally would not indicate response to immunotherapy, but this is a different way the cancer could be expressing all kinds of weirdo proteins.
So, I was re-reading about the trial WeareOne brought up earlier, NCT03970382, which is offering to actually sequence the cancer to look for neoantigens and then engineer T cells to go after that and test it as a vaccine alone or in combination with immunotherapy. They are doing this for several different cancer types, and HR-positive MBC is one (the one least likely to respond but kudos to them for trying). When we discussed it before, this trial was only in California, but now they added sites at Fred Hutch in Seattle, Memorial Sloan Kettering in NYC, and Northwestern in Chicago:
https://clinicaltrials.gov/ct2/show/NCT03970382#co...
PS They seem to be open to stage of treatment, open to anybody after first line or if they are at the point of no other options; They also seem to be seeing neoantigens in lots of tumors, so there must be multiple ways cancer cells have to screw up, not just by mutating DNA repair proteins
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Hi Cure-ious,
The numbers for the Veronica trial seem odd to me as I recall from my reading that the PFS of Fulvestrant is about 8 months. I was on it for 21 months before I added Verzenio, primarily as I felt I was pushing the limits of the Fulvestrant and I figured I had a narrow window of access to the Verzenio given when it was approved in Canada and where I was in terms of disease. It held things steady throughout. I had about 10 months on the two treatments before subtle signs started to indicate things were starting to go sideways despite stable scans. It was another five months before it became clear with progression to the liver.
Odd that they got a PFS of 1.9. Was it a heavily pretreated subgroup
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Hi Cure-ious,
Sorry,I have no updates on these clinical trials. I am keeping an eye on the Pact Pharma (NCT03970382) updates but looks like they have been quite for a while now.
I checked with Dr Rugo on NCT03970382 ,but she does not seem to be excited about this clinical trial.
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Sadie, Sure there is a lot of variation and that's why they do the control each time, most likely the group had been more pre-treated, as you suggest, I'm glad you pointed out that depending on the situation, one can indeed get a long time on Faslodex alone!
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hi all!
I've been on the trial drug Tomivosertib for 3 weeks and had my first paclitaxel infusion on Tuesday. Had a Anaphylaxis reaction instantly to paclitaxel, the moment it went in my port. It was so scary to one second able to breathe and next not. Anyway they seem to still want me to carry on with chemo, with extra pre-meds like a second dose of benedryl, steroids and something else that I can't remember the name of.
I sure hope this works after all this. I am still recovering from the 3 liver biopsies, gawd.
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GG27 Oh my That was so scary. I have heard of others who had reactions to chemo- they stop it, add benadryl and a steroid then start it back up. Kill the cancer!! But remember the patient please.
Dee
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saw this while cruising ASCO. I think our MOs could be more proactive in expanded access to trials with help.
Dee
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So, I heard back from the Johns Hopkins virtual clinical trial, and here is more info for those who may have SF3B1 mutations and be considering this.
The conditions of the trial are that: 1) when you have progression, they send your information to their tumor board. Their tumor board can recommend you try some immunotherapy, and if so, you have up to 4 weeks to respond ; 2) You do that by getting your insurance or the pharma to supply a checkpoint inhibitor, and 3) your MO gives it to you as a monotherapy. I don't know how long you would keep taking it (presumably for as long as you might be stable) and 4) they collect some blood samples before and after. Like any trial, you can drop out at any time. Trial does not require measurable mets, bone-only is OK.
So one possibility would be to try some immunotherapy before moving over to clinical trial giving a SERD or PROTAC. The problem with immunotherapy is that to be effective, not only does the cancer need to look screwed up by expressing lots of surface neoantigens, but also we need to remove the shielding cells that the cancer uses to hide from the immune attack. The SF3B1 mutation helps by providing the neoantigen part, but there is nothing to help with the unshielding part. Nevertheless, it is a way to give immunotherapy a shot...
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Cure-ious, I may have missed this somewhere, but would an SF3B1 mutation be on my FoundationOne report? How do we know if we have this?
Thank you for sharing all your knowledge here.
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Buttons, yes, Foundation One picked up my mutation (SF3B1 R625L); the SF3B1 K700E variant is a more common one, but either one is in the hotspot area where the mutation affects its activity (and so produces neoantigens)
But whether I try it or not will depend on how things look at progression, it seems immunotherapy alone would still be unlikely to work, might wait for a combo trial. I hate how all these critical decisions are made with no biomarkers, scans or other data and often without even any informed input, based on experience...
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