Are you currently (or have you been) in a Clinical Trial?
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Hey Frisky, I’ve got expressed this sentiment before, but thanks for giving this a shot! Every big medical breakthrough is the result of many many people stepping up. This thread is invaluable and i share it with my mom regularly
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skyfly I wish you and your mom the best of luck!
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Frisky, it sounds like you made the right decision for yourself. Onward and upward. Praying for an opportunity to come along out of left field.
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So not exactly sure where to post this, but I received my Foundation One report today. Aside from the fact that I can't understand all of it (or even most of it) the most shocking thing to me, with ILC that has consistently tested ER & PR positive and HER 2 negative, is that in the first two pages, the report talks about two startling things: 1. The report says that I have a very high number for the "tumor mutational burden" -- 25 mutations. The sole FDA approved therapy is Atezolizumab (trade name Tecentriq), which is an immunotherapy drug. I don't think I've ever even heard of this drug? 2. The report says that I have an ERBB2 mutation, which, if I understand it correctly, means that I have some sort of a mutation that predicts sensitivity to therapies targeting HER2.
I am blown away by this. I haven't seen anything on the boards about what was an ER/PR +, HER2- tumor changing so that these treatments would be feasible? I have seen stuff about cancers mutating to triple negative, but that's not exactly what this says, I don't think. My onc has started me on faslodex, based upon my path report, with a start with Ibrance next. But that doesn't show up in this report at all.
I would love it if anyone who understands this stuff even a little would weigh in and explain what the heck is going on here? Thanks so much.
Bev
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BevJen, in a sense, you are "lucky" to have such a high tumor mutation burden as it does mean that you are more likely to respond to immunotherapies. I believe Tencentriq is on the newer side. With respect to the ERBB2 mutation, this is different than the amplification that is tested when you think of someone being HER2 positive or negative. One can be HER2 positive or negative with an ERBB mutation, which means there is a HER2 activating pathway (I believe there are a few ERBB mutations, including 2, 3 and 4). This could also be good news in that you may respond to HER2 drugs. There is a recent one specifically targeting ERBB2 and other related mutations called Neratinib.
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Yes, what JFL says. You now have at least two more therapies in your arsenal and neither one is chemotherapy. You might want to hold off on the faslodex briefly so as not to disqualify yourself from the trial that has Faslodex and neratinib.
ClinicalTrials.gov Identifier: NCT01670877
Neratinib +/- Fulvestrant in Metastatic HER2 Non-amplified But HER2 Mutant Breast Cancer
As I understand it the usual Herceptin, for Her2 positive/amplification is not what you want for an ERBB2 (aka Her2) mutation. You want neratinib, whether in or out of a trial.
Or look into an immunotherapy trial.
ERBB2 mutations are not uncommon in relapsed ILC.
And perhaps the high mutation number indicates that you may have the immune-related subtype of ILC going on. (For a very technical paper on ILC subtypes, see
Ciriello G, Gatza ML, Beck AH, et al. Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer. Cell. 2015;163(2):506–519. doi:10.1016/j.cell.2015.09.033 )0 -
JFL and Shetland Pony,
Thanks so much for you insightful comments. I really appreciate it. Now I have some things to discuss with my MO, since I'm not so sure that I should be doing Ibrance and Faslodex after all. First things first -- on this coming Friday, I am having a microwave ablation of the 2 cm lesion on my liver. After that, we will have to determine the appropriate drug to be on.
Bev
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BevJen-- Its not uncommon for ILC to gain mutations in HER2 as the number or length of treatments acccumulates, especially anti-estrogen treatments. This is different from amplifications in HER2 ("HER2+"). In HER2 amplifications the HER2 genes are normal, you just have more than the typical number of them, so their effect (drives cell reproduction) is amplified. In HER2 mutations. you may have the typical number of HER2 genes, but those genes are mutated-- the mutation may or may not result in an increased signal form those genes. There is some evidence that mutant HER2 can respond (in some cases) to the anti-HER2 meds, but that is not yet proven. It is certainly worth trying Neratanib. (Although be forewarned that there is a lot of diarrhea associated with it-- manageable if you get on top of it early, but it can be problematic.)
Did your F1 report identify any ESR1and/or Rb or CCND1 or 2 mutations? If not, then fulvestrant and Ibrance would be a good option, too.
25 mutations IS high for ER+ MBC-- I would definitely suggest that you look at immunotherapy and IO (immunotherapy) trials..(Atezo is an anti-PD-L1 drug.) There is not much evidence that single-agent PD-1/PD-L1 meds will be effective, so you might want to consider it with something else (i.e., a trial). Although with that degree of mutations you may get a better than anticipated response to single-agent Atezo since you have an unusually high number of mutations. The GELATO trial in the Netherlands is using Atezo with carboplatin for metastatic ILC.No reports yet of results.
I am just in the early stages (2 weeks=two every-other-week treatments) of an IO trial with Nivolumab/Ipilibumab/bicaluatmide (PD-1/CTLA-4/ anti androgen) clinical trial for my ER+/PR- lobular MBC...it's pleomorphic and I have 9 mutations, most of unknown significance, which the PI's consider "a lot" for ER+ MBC. Christine Desmet (a researcher who studies ILC) has told me that she believes pleomorphic ILC will be response to IO--it's just that it is not a common variant, and she doesn't have access to sufficient samples to do a meaningful analysis...
I can't comment on the efficacy of IO for ILC--I won't have scans for another 10 weeks, so allow have to go on is my slightly-falling CA27-29 and the fact that I have developed a rash (many people get rashes on IO, and not all of them have a positive response; but nearly everyone who does have a response gets some sort of a rash, so at least I'm starting off in the 'right' group!) So far it's been very easy- I don't have any of the other side effects (nausea, fatigue, joint aches) common to IO, and none of the severe autoimmune symptoms have appeared (yet) either. But it is early....
Let us know what you decide to do.
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I should have added to my post that your oncologist’s idea of Faslodex and Ibrance is not necessarily a bad one. Faslodex can work when other anti-estrogens have failed. Xeloda is another standard option. It will be important to discuss your options and your F1 report in detail. If it shows mutations associated with failure of Faslodex and Ibrance, that is important.
In my own case, my Guardant liquid biopsy showed an ERBB2 mutation and suggested neratinib, but we decided to keep that in our pocket for the future and go with standard options. Faslodex with afinitor for four months did nothing for me, so next we tried xeloda, which has kept me NEAD for two years.
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Elizabeth -- Good to hear that your trial is going well so far. I hope you have great results! You asked if the report showed any ESR1and/or Rb or CCND1 or 2 mutations. The answer is no (I actually expected an ESR 1 mutation to show up.) F1 showed ERBB2; PIK3CA; CDH1 and MAP3k1, plus the note about the 25 mutations under "tumor mutational burden."
Shetland Pony -- once again, thank you. My report also shows neratinib plus some other things for the ERRB mutation; shows alpelisib and everolimus for PIK3CA mutation; and, as Elizabeth noted, Atezolizumab (Atezo) for the high tumor mutational burden (but damn, that GELATO trial in Holland requires that you can speak Dutch!)
I will let you all know what happens. I think my oncologist is a BIG fan or faslodex (since I failed letrozole after 16 years on it!) along with Ibrance.
Thanks much!
Bev
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JFL, Thanks so much for a list of the chemos you have been on in order of difficulty. I know we are all different in the way we react to different treatments but more information is always better, I believe. Also, thanks to you and EV11 for explaining the difference between HER2 amplification, HER2 mutations and ERBB2 mutations. I have an ERBB3 mutation. Doesn't seem to be anything targeting that yet.
I had my second Abraxane infusion yesterday and it has been so much easier than the regular Taxol. All of my side effects were because of the premeds so no insomnia (from the Dex) and no restless leg syndrome (from the Benadryl). I am doing ice packs on my feet and hands and hope this will keep away any neuropathy. Actually feel great. Hope it's working.
Was looking at adding Avastin. There was a trial comparing Taxol alone or Taxol + Avastin. The combo doubled the PFS (6 months to 1 year) but didn't change overall survival. Apparently, after those trial results, Avastin is no longer indicated as a treatment for breast cancer. Has anyone been on that trial or taken the combo? I once had it injected into my eye in an attempt to treat my eye tumor but it didn't seem to do anything. Also, my eyeball became hugely swollen, like a baseball, and completely red. Didn't know your eyeball could get that big.
Hugs, Susan
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BevJen-- I actually asked the GELATO PI if I were able to re-locate to Amsterdam would I possibly be able to enroll? I have very good friends who live there who would would shelter me and my daughter for the duration of the trial....She said if I were willing to hire an official Dutch-to-English translator to go over the consent with me I should be eligible-- there is no exclusion for Non-EU members (at least when I asked her this question almost 2 years ago this was her response--many things have changed with the Brexit fiasco, so you would definitely need to confirm non-EU enrollees are permitted.) Or you could petition Genetech to provide Atezo under compassionate use and have your doc prescribe the chemo portion...Youmight want to spend some time looking at the trial options that are out there, and search for meds that might be coming to trial soon-- many of them are paired with fulvestrant and prior use may preclude your enrolling in them. But not having an ESR1 mutations should confer susceptibility, so you might just want to jump on fulvestrant right now and let the future trial options fall as they may. I finished 3+ years on Ibrance/letrozole without an ESR1 mutation, but 9 months later, after 8 months on Xeloda, I developed an ESR1 mutation....now fulvestrant is a less-compelling option for me...go figure. I deferred Fulvestrant and started Xeloda after I/L waiting for a trial that was going to open to get to the recruiting stage. So much for my planning!!
SusaninSF-- Neratinib was found to be effective against HER3 in the SUMMIT trial, and there are a few trials actively enrolling for anti-HER3 meds-- here's one that requires 2-6 prior lines of chemo, include a taxane--keep it in mind for when/if you need to move on from abraxane:
ClinicalTrials.gov Identifier: NCT02980341
https://clinicaltrials.gov/ct2/show/NCT02980341We have lots of reasons to be hopeful-- just have to be on the lookout for good trial matches; there are so many trials and our once have so many patients that its really up to us to do the searching.
Hope you all are feeling well and finding moment of joy in your days...
Elizabeth
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(Cross posted in TNBC stage IV and people with liver mets threads)
Hi everyone. Posting here because this group's collective knowledge and wisdom is incredible. Hoping some of you may have some nuggets of info or suggestions that will guide my next step. I've included a brief history at the bottom of my post, in case that's helpful.I just found out that Gem/Carbo is no longer working. My PET/CT shows two new liver tumors and previously inactive or less active bone mets are very active again. My cancer seems to behave unexpectedly and aggressively, so I want to move onto a next line quickly. I didn't start chemo last week, as I don't want to jeopardize my eligibility for a trial, should I find one that is promising in the next few days. My questions:
- For those of you with TNBC liver mets, what chemo did you use as a next line after Gem/Carbo? Was it successful? It seems consensus is that I should do Eribulin (Halaven) next. Experience with that? (And did you lose your hair?)
- Anyone know of any interesting immunotherapy trials? I am not currently a candidate for the NCI CAR T trial, as my liver met is not easily resectable. I am looking into both the MSK CAR T targeting mesothelin and the Fred Hutch CAR T ROR1 studies. What am I missing? I don't want to do any PD1/PDL1 drugs due to a MDM2 mutation I have that is associated with hyper progression on Keytruda.
- Other ideas? My current plan is to biopsy before starting a new treatment, but I will find out this week what the wait time for a biopsy is.
Brief history:
- Dec 2016 diagnosed (just postpartum) Stage 3 ER/PR+, HER2-
- AC - Taxol. Mastectomy. Radiation + Xeloda (as radiation enhancer). Ibrance/faslodex/lupron (due to remaining live cancer at time of mastectomy)
- Jan 2018 2 liver mets. TNBC
- Gem/Carbo got me to NED by April. Scans clear July and Oct, so I stopped chemo.
- Jan 2019 cancer back in my liver and spread to bones.
- Restarted Gem/Carbo. April scan showed metabolic resolution in liver. All bone spots less active or inactive
- This week shows 2 new liver spots and bone spots active again
Thanks so much to anyone with an idea to offer. This group is incredible
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Information for people looking for immunotherapy trials who have a resectable tumor: last evening I wrote to the study team at NIH/NCI in Bethesda, MD. regarding their immunotherapy trials that are ongoing. That is where breast cancer patient Judy Perkins, who had failed both chemo and hormonal treatments, was treated in 2015 and so far she is free of cancer from the reports that I've read. Anyway, this is the info that I received back, and because it says some stuff that I wasn't aware of, I wanted to pass it along in case it would help someone else. I've already begin Faslodex, and this coming Friday I will have a microwave ablation of the largest lesion in my liver, so I can't take advantage of this right now -- but the next time a treatment fails me, I am going to consider this, even though it's scary stuff. Here's what they said:
"Thank you for your interest in our clinical trials.
We screen patients at the point of disease progression during that small window in time before they begin another line of therapy. We would review the doctor's notes, reports & scan imaging looking for a discrete metastatic lesion, 1 -2 cm in size, we can easily resect though a small operation. If our surgeon sees such a lesion, we would invite the patient to come for a screening visit. We would then resect the lesion, take it to the lab, extract the lymphocytes and grow the lymphocytes into billions of Tumor Infiltrating Lymphocytes, or TIL cells. The tumor would also be sequenced for mutations. The goal is to create a cell therapy which would target the mutations within the patient's cancer. Unfortunately, this process takes us 3 - 4 months. A patient can go onto another line of therapy during that time. The patient would need to be off all therapies for 30 days prior to resecting a lesion and for 30 days prior to treatment.
As you are considering clinical trial options, please note that treatment with some of our trials may require a 3-4 week stay at the NIH Clinical Center in Bethesda, MD. While this is a form of immunotherapy, it also typically requires pre-treatment with traditional chemotherapy (cyclophosphamide and fludarabine) to reduce a patient's lymphocyte count prior to infusion of the cells."Hope this is helpful to someone.
Bev
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Thanks, Bev. I have kept an eye on that one as well. I reached out to them a few years back and received about the same information. It sounds like they haven't adjusted their protocol much if at all. What is frustrating about trials is the wait periods where one cannot be on treatment. However, sometimes, we have no better options. I am hoping to see more success stories out of this trial. This trial is no joke though. Judy was "cured", while one of the other breast cancer patients died during the period where the NIH wipes out one's immune system with chemo prior to reinserting the TILs. She went into sepsis and didn't survive. There was a third breast cancer patient that made it through the trial but it didn't ultimately work and she died a year or so after the trial. I haven't heard any additional updates about new breast cancer patients but would be interested to hear if there have been others. Perhaps someone here has more information.
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Any updates from those of you on this trials thread?! Hoping there's been good news for everybody!!!
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Hey Cure-ious,
I'm still in the trial and about to start my 8th cycle, but it may be my last. Although I've continued to make steady progress in my targeted tumors (44% decrease since December), my last scan in early June showed that my liver appears to have progression. I had a liver biopsy and the hope is that it is pseudo-progression - inflammation. I won't know for sure until my scans in August. I'm still feeling great and my blood work has been fine, so I'm not freaking out.
You (I think...) had asked me a long time ago about which mutations I have. I have ESR1 and FGFR1.
I've been assured that they have a few other trials to offer me if this one goes south, but I will update everyone in August.
Thanks for asking...I just haven't felt like talking about it.
Katty
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Hi there. I'm not on a clinical trial but I've been following this thread with interest and trying to learn - I don't understand a lot of what you all discuss but I try. I am on a non-standard protocol so I thought this may be as good a place as any to post - I've not actually seen anyone else currently on the same treatment so feel a little alone. I've recently started on a combination of Herceptin and Keytruda. I'm strongly HER2+ and had a good run of nearly three years on Kadcyla albeit with two different SBRT interventions to beat back progression. Now, after a third small but clear progression we decided it was time for a new systemic approach. Was also seeing elevated liver test numbers so think I was reaching drug toxicity with Kadcyla because scans showed no evidence of activity in my liver. Anyway, I was offered a standard chemo combination (can't remember just now what it was) or the Keytruda - due to high tumor mutational burden - so I opted to give Keytruda a whirl. Too soon to know whether it is working but I feel pretty good. Still have a bit of pain in my lumbar region no doubt due to the lesion in my muscle but finally feeling less fatigue than I felt on Kadcyla. Will have blood tests later this week before second infusion so will see how things are looking. Sorry if this is inappropriate place to post.
Marg
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Hi Marg,
I started this thread and all are welcome. I have learned so much from women in these forums, even if we don't have the same protocols, so again, welcome!
Your treatment sounds really interesting and I hope it provides great results! I think we'll all be following your progress with interest!
Katty
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Katty, do you also get tumor markers as part of your blood test? Maybe that will give you an idea of whether it correlates with whats going on with your liver. Thanks for letting us know of your mutations. I also have FGFR1. I hope that its just inflammation and this trial works for you for a longer time.
Hugs,
Ann
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I am still on the BYLIEVE trial now on the fulvestrant arm only. CT scan on Wednesday which will confirm whether my liver met is indeed growing or not. The trial police (ha ha) wanted me off the trial last scan as the radiologist indicated that he thought my tiny tumour had grown but my MO challenged his finding. I think he's correct but hoping he's not. My CA15-3 has been rising by tiny amounts (1-4 points) over the months. I think my MO is trying to keep me on this trial til the oral fulvestrant trial opens in Vancouver, so some reason it's been on hold since May1.
cheers, dee
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Katty, Well, there are many stories of pseudo-progression on immunotherapy, so good thing that they are checking closely to figure out what is happening ! If nothing else, you got eight months of healing and reduced tumor burden, along with a reprieve from chemo and drugs- and studies show that responders have stronger and longer benefits from subsequent therapies. If you have to change it up, it will be interesting to see what else they recommend, whether you are to continue on immunotherapy regimens, etc. And otherwise, this may just be a blip in the road..
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Thanks, Katty! Also hoping to hear that any progression you may have is the pseudo kind!
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Thanks all! Marg, yes I do get tumor markers and there hasn't been any radical change. Cure-ious, I share the same sentiments as you've expressed.
And, I assumed that with the progression, I'd be immediately kicked out of the trial, but in actuality, there is some leeway regarding progression in this trial's protocol. Continuing in the trial with progression is at my doctor's discretion, hence the new tests and at least one more scan. We shall see!
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plus another benefit to the immunotherapy is that its not (as I understand it) putting pressure on the cancer to mutate and become more aggressive, the way drugs do- and in the same vein, you don't become "resistant" to immunotherapy, so it does not preclude you from future combination trials that use it. If it stops working, it might be that the immune cells got "exhausted" from the boosting, and so you need something to reset this, or some drug combo to unmask the cancer and expose it better to the immune system
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GG27 - I hope that Faslodex alone continues to work for you. I'm glad to know that you have an MO who is willing to fight for you! Last week, I started the Phase 1 oral SERD trial of G1T48 by G1 Therapeutics. There are a number of oral SERDs that are being investigated in trials. One oral SERD is in a phase 3 trial. I've had no side effects after 10 days on the drug. The first patients received 200mg/day and my group is taking 800mg/day. The trial will continue to add patients at increasing dosages until patients experience unacceptable side effects or they reach 2000mg/day. I will be scanned after 8 weeks on the trial. Which oral SERD trial are you considering in Vancouver?
Katty - I'm following you and your trial closely. I hope that you continue to respond and that future treatments will work even better after the immunotherapy trial! Thanks for sharing your experience!
Hugs and best wishes to all!!! Theresa
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Theresa45- interesting news about your trial. are you doing this at Stanford or UCSF? I am very hopeful about oral faslodex.
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Nkb - I'm in the trial at Stanford. It would be wonderful if one of the new oral SERDS is able to get around hormone therapy resistance, particularly the ESR1 mutations that develop when treated with AIs!
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Hello, all you smart cookies. I am jumping in with a question. This week I will have a biopsy of whatever is restricting my bile duct. If it turns out to be an ILC met, what genes should I be sure to have included in the genomic testing? I think the tests can be customized at the onc’s request. I’ll make sure they do MSI testing. What else that might not be standard with all companies?
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Shetland-- lobular tends to develop PI3K/mTOR/AKT (lots of trial drugs and Piqray would be options) and FGFR mutations (one sort-of-promising trial med); less commonly, but more frequent than in IDC are HER2/3 mutations; and occasionally HER2- cancer will become HER2 amplified (equivocal or amplification is determined by histology, so in addition to genomic information be sure to get ER/PR/HER2 IHC testing as well.) Anyone with a significant time (more than a year or two) on an AI and or fulvestrant can develop ESR1 mutations (the oral SERDS might be useful here.)
About 20% of ILC (and closer to 40% if Luminal B/PR-) are "Immune type" and so PD-1/PD-L1/CTLA4 testing might be informative. IF your are MSH high or have PD-1/PD-L1/CTLA-4 markers you might be a candidate for immunotherapy. (I'm getting my third dose of Novo tomorrow as part of an Ipi/Nivo/Bicalutamide trial...not clue yet about how well it's working-- it's only been 4 weeks.)
I have a note at my desk to do some lit searches tomorrow when I have a few minutes regarding ILC mets to the bile duct. It's more likely than primary bile cancer...but I'm glad you are getting a biopsy.
If you send your tissue to Foundation One the genomic tests mentioned above are all included; I'm not sure which (if any) of the immune checkpoint-relevant tests they run as standard. I'm sure you can get that information from their webpage.
I'm glad that you are doing testing. I think it helps to give a bit of insight about how your cancer cells try to evade treatment. Hopefully you learn some useful bits of information. Please let us know what you find out, and what you decide to do....
Take care, try not to be TOO stressed, and may you find a moment of joy in each and every day.
Elizabeth
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