Are you currently (or have you been) in a Clinical Trial?
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Nicole, remember that study I posted a while back? It's more likely to lose markers than to gain them.
phet, I was in 1 trial for about 8 months and another trial I ended up dropping out of. My gentle observations is this: reality is we're trying to postpone the inevitable. I mean we can hope for durable remission, for being a super responder but we have to be prepared for the probably outcome, which is buying an extension. So the question underlying some of these decisions has to be - if worst comes to worst, where do you want to spend your last years? Where will you feel comfortable and safe and happy? btw, my first 3 months on the Roche trial were hell. I was very ill - waaaaay sicker than I had been before the mets dx. It's been way better since but at any time, I figure it could slide backwards again & be that unwell again - where would I want to be?
Trials are also very time intensive. Lots of extra tests, extra lab work, extra interviews, long protocols, long lists of what you can & can't do etc. & that's all assuming that you don't have a weird reaction to the meds or one of the life threatening side effects etc. And in early stage trials, there's a lot more risk of adverse SE. So where would you like to be IF that were to happen?
I thought about seeking trials somewhere else but between covid and just the extra disruption of going places etc, I think at this point I'd be very reluctant to go far. For a 1 shot deal like SABR or CAR-T, maybe. Otherwise, I'm not sure I'd pursue anything outside of a couple hours radius.I hope you can line up a treatment plan somewhere soon which meets all your needs!
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Moth...yes I remember you were right. I read up on FB even more evidence of that...
. I am more likely to go TNBC.... bc I am ER+ PR- HER2-....0 -
Moth- very good points, I think of them a lot. where do I want to be- I prefer to "go gently into that good night" if I get a choice.
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Moth, I absolutely see your point. I think the reminder of how tiring and intense trials are is important and I need to remember that. In terms of where I want to spend potentially my last year/s - this is a tricky one for me. I live in the UK where I have friends but the idea of being home in Australia is also appealing, as is being in Italy my surrogate home via my partner (and where we have family and friends too). Work would be tricky if I left the UK but it might be tricky re treatment anyway. This is one of the reasons though I'm trying to be quite open to those three geographic options - all have emotional/personal things to recommend them as places to be based.
I've been in touch already with the trials team at Barts in London and they got back to me straight away and are already communicating with my team in Oxford. I still have some diagnostic issues but I'm half hoping a trial's need to know exactly the histology of my cancer before starting will help me push forward with getting answers to those. I just really want to move forward with treatment, but am determined to look into all options and make an informed decision even if it takes a bit more time....
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Hi all - in my research into trials I've come across one combining Keytruda with Lenvatinib. I'm not sure I would look into it for first line treatment as I'd like some chemo in there for first line, but I'm curious if anyone has come across trials/research related to Lenvatinib (or related drugs) with breast cancer before? any thoughts most welcome!
This is the trial: https://clinicaltrials.gov/ct2/show/NCT03797326?term=nct03797326&draw=2&rank=1
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my Roche trial was for another kinase inhibitor, ipatasertib, + immunotherapy (atezolizumab) + chemo.
I know someone else on a similar trial combo but I haven't heard of anyone yet doing it without a chemo in the mix. I guess they're trying to figure out if the chemo backbone is needed.... I'd personally be more like you and inclined to want chemo in the mix but I guess we need the studies to sort out what is doing the heavy lifting in these treatment combos
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thank you moth that’s very helpful! I know some people on that trial at Barts in London too but it’s not recruiting any more, otherwise I’d be putting my hand up
there is a trial where I might have a chance of getting capivasertib with durvalumab and taxol, but I could also be randomised to just the immuno and chemo (not that I’d be complaining) or those two with olecumab (?) Thekinase inhibitor is very appealing so I will talk to my trials team about my best option for that with immuno and chemo 0 -
Phet....it doesn't look like you are TNBC...do you have PDL1? The trial you listed states ya have to be TNBC
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Dee, good luck with your new trial. You have been able to move on a few trials pretty quickly lately. That is great.
I have been taking Enhertu for HER2-low for a bit over 3 months/4 cycles and was in pretty bad shape when I started the drug. I have had pretty dramatic results and it is really taking care of my liver mets well. As a reminder, I am not in the DESTINY-4 trial for HER2-low, nor any of the other HER2-low arms in the DESTINY trial (didn't qualify given the number of prior treatments). I am taking Enhertu off-label. However, I thought it may be helpful to post an update here in case anyone is considering an Enhertu trial for HER2-low. After the first cycle, my liver enzymes, alkaline phosphatase and two different tumor markers, including one that never moves out of normal range, shot up to all-time highs. Likely massive tumor die off. However, since then, they have all been dropping week after week as Enhertu is shrinking my liver mets and they are nearly all metabolically inactive now. I still have non-malignant ascites but it is improving and I am hoping it goes away soon. The ascites was caused by a hepatic vein thrombosis likely triggered from a combo of the liver mets and Faslodex. So, I have to wait for the thrombosis to resolve more or for my veins to improve the rerouting process they go through in the event of thrombosis. I was having up to 5.7 liters drained weekly and am now down to 2-2.5 liters every other week. Belly was looking 9+ months pregnant and diuretics weren't helping at all. Now, belly looks anywhere from 4-6 months pregnant and the diuretics definitely help keep things in check a bit now. The only recent complication from the ascites is that the fluid has started to leak into the pleural space so I also have a bit of non-malignant pleural effusion which causes some shortness of breath and discomfort. At first, I was worried I was developing pneumonitis or interstitial lung disease, a known side effect of Enhertu. I was actually relieved it was a pleural effusion because usually one would be taken off of Enhertu permanently if one develops symptomatic pneumonitis or ILD. If it is asymptomatic (found on scan without symptoms), then one is taken off of Enhertu temporarily and given prednisolone until it resolves. I never knew it was possible to develop pleural effusion in the absence of love lung mets. So strange.
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JFL WOW so happy for you!!!!! You can now have hope to get ALOT of long years to come...most HER2+ (even though you are low) get sooo many years its amazing and it looks like you respond to HER2+ treatment so that is great!Thanks for keeping us updated.
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JFL- Thanks for the detailed info about your experience with Enhertu. So glad you are having a good response!
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That is great to hear JFL, and very promising results for others in a similar situation. My wife had a similar ascites occurance when xeloda started working on her liver mets. As the mets started to die, the ascites developed, along with hepatic hypertension, varices, enlarged spleen and probably other stuff I've since forgotten.
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Phet, you were talking about choosing UK, Australia, or Italy as the choice relates to clinical trials, and moth brought up the idea of where you would most like to be no matter how things go. I will add this thought: Clinical trials aside, which place gives you the best access to the most promising therapies outside of trials? In other words, which place has the fewest “but that isn’t approved/available yet here” responses when you look at a list of good treatments?
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JFL, I’m so glad to hear of your success, and that the other “issues” are figured out and being managed and watched appropriately. This is one heck of a story.
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JFL: I am new to this game but happy to hear of your success! It sounds like Her2-low is something all our oncologists should be checking as well
Nicole: I haven't updated my signature line yet because I still don't have all the details on my secondary diagnosis
It's a long saga but basically the only biopsy-able place (one of my mediastinal nodes) returned an inconclusive result - I have cancer but they can't say which one. It can say it's hormone negative though. My team is saying we assume (!) it is recurrence of breast as other obvious ones - like lung primary or gastric or gynae mets - are excludable according to histology. My original cancer was Her2-neg - that result is due this week but we are assuming negative again as it doesn't usually switch. So I'm looking at TNBC mets basically. I am curious whether ER+ cancer that loses its hormone receptors on progression should be treated differently than original TNBC primary (I think one of the things that has confused my pathology is this weird mutant form I am now) but it seems at present I would now be treated as TNBC. Cure-ious wrote upthread somewhere that ER+ that turns to TNBC responds well to immunotherapy so I'm hoping so. For the science-y out there, what appears to be confusing about the histology of my mets is that they lost GATA3 expression (highly correlated with hormone receptivity, so that loss may even be the 'mechanism' for my hormone negative status) but did not gain p40 (a marker of basal-characteristics). And what really threw them - they are CK7 positive - normal for breast cancer - but also CK20 postitive - not normal for breast cancer. CK7+/CK20+ is the usual pattern for gastric or ureothelial cancers apparently. But luckily we can exclude mets from an occult primary from there by the fact that I lack other necessary biomarkers for that. So I'm a freak with my strongly CK20 positive breast cancer which apparently is very rare and is the case usually only in very unusual breast cancers like medullary or apocrine, neither of which I had.
ShetlandPony - yes that is a very good point too and I've thought about that. I need to do more research on it. The UK tends to be slow with drug approvals because of the very bureaucratic process of negotiating a deal between the NHS and the drug company to make it affordable on a completely government-funded system. For example Trodelvy is not approved yet. But they do usually get around to approving things. I need to look into Australia and Italy more - Australia is a rich country with a very well-funded system so I would like to think they would be quick to approve new treatments but I just don't know. Mu mum is organising a private referal to a top Aussie breast oncologist for me, hopefully asap, and I will ask them about that. Italy is a basket case in many ways but they have a surprisingly functional health system usually. And of course the longest life-expectency in the world alongside Japan, which I would think bodes well for their ability to treat cancers? My mother in law is meant to be researching a fluent-English speaking top Italian oncologist for me to speak to and ask exactly these questions! But it's a very important consideration
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Hello all - I just got my Foundation One liquid biopsy results and am poring over them of course. Lots in there for me to research...but crucially, the one clinical trial that is both in the UK, currently recruiting and was recommended on it is one I mentioned earlier with Keytruda and Lenvatinib. Today my oncologist has said that with Covid bearing down again my hospital (Oxford) is not recruiting for clinical trials at the moment and she fears others will be the same. So she's proposing putting me on Gem/Carbo to hit the (now confirmed) TNBC hard and then we look for a trial in the Spring. I'm not sure how I feel about this as I am very keen on immunotherapy.
According to the foundation one I have an intermediate tumor mutational burden (bTMB 8 muts/mb), MSI cannot be determined, and quite a few mutations: EGFR amplification, FGFR1 amplification, AURKA-amplification (equivocal), MYCN amplification, ESR1 amplification, CASP8 alteration, ETV6 deletion, NSD3 amplification, RB1 alteration, SPEN rearrangement and TP53 alteration. If anyone sees this and a clinical trial jumps out at you let me know!
One thing I don't get - why do I have ESR1 amplification if I lost my hormone receptors on progression? Strange
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Phet7178,
I've read a lot about immunotherapy in the context of non-TNBC. In that context, they look at TMB a lot. For example I am ER/PR+ and HER2 negative, but under our FDA guidelines, because I have high tumor mutational burden (25 mutations) I am eligible for keytruda by itself. I'm wondering if your intermediate tumor mutational burden, coupled with your TNBC, would give you a good boost from immunotherapy.
There is an organization called the Cancer Research Institute (online info) that does a lot of work promoting immunotherapy. You might try perusing their website and looking at their videos to see if you could contact one of their researchers to ask questions about immunotherapy trials.
Also, here in the US, you can go into the website for clinicaltrials.gov and search your mutations to see what trials are out there. A lot of the trials that I've looked at on that site have trials going on in other parts of the world. So that may be helpful to you, even though you are not in the US.
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Phet I am also TMB Intermediate..unfortunately that doesn't seem to make a lot trials that are for Immunotherapy (TNBC) accept me
. but you might have a better shot since they are saying you ARE TNBC...I also don't understand why you have ESR1 if you are not HR+ I have that one but I am ER+ PR-.... maybe you do still have some parts of tumors that are ER+?? Hopefully Cureious or Moth will chime in they know a lot more than me...
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JFL, You have been at this unwanted journey a long time, 2006! So glad the enhertu is working. 🙌🏻
My liver enzymes rose to 2x normal on Monday. Quite high for me. Wanting it to be tumor die off. Your story gave me hope. Trial nurse said if they continue to go up they may pause the drug.
So far ARV-471 is giving me typical serd SE. Achy joints, hot flashes, some fatigue. Trying to get out for a daily walk. My LE cording in the right axilla has also flared. ROM in that arm is painful. Working with my therapist.
I had 9 adult children and spouses and 1 grandchild for several days. Such a blessing. we were all very careful and wore masks the whole time. Resting these past couple days has been the standard of care. 😉
Happy New Year everyone
Dee
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JFL ..I wanted to mention...one of the things weeks / months ago that could have made your liver enzymes out of control was the mebedazole....it made my ALT AST quadruple....it took over 2 weeks to get down
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AlabamaDee, do you have the option to undergo a scan before being pulled off the drug due to escalating markers? I seem to flare to some extent when I start most drugs although the flare on Enhertu has been like no other!
Nicole, good point about mebendazole. When my bilirubin and liver enzymes skyrocketed, I stopped the COC protocol and most other supplements. I have recently added metformin back into what I take but none of the other COC medications. I figured metformin will help keep my liver size in check a bit - won't get as big if it can't store as much sugar. It is funny - on my PET scans now, areas of my intestines light up but it is due to metformin "arresting" some of the sugar I eat in my intestines. It is not even mentioned on the scan as this is a known presentation for those on metformin. When my liver swells after each Enhertu treatment for a few days, everything gets more cramped and my belly gets bigger. With the ascites, pleural effusion and pressure from blocked hepatic vein, there is no room for my liver to swell. Livers can grow 50% throughout the day to temporarily store glucose not used immediately by the body and other nutrients. About me having success with other HER2 treatments - that is a big unknown at this point and others are not approved for HER2. Most have not even been studied in HER2-low patients and a few that have been studies have not produced promising results. I hope it is the case that other HER2 treatments could work but antibody drug conjugates (ADCs) like Enhertu combine the immunotherapy aspect of herceptin with potent chemo, exponentially more potent than the drug (a topimerase 1 inhibitor) would be if taken via infusion. The form of the topimerase 1 inhibitor in Enhertu permits it to uniquely permeate surrounding cancer cells that do not express HER2 at all and as a result, has the benefit of causing collateral damage to surrounding tumors via the "bystander effect". Not sure if a non-ADC that didn't work in the same way would produce the same results.
Phet, I don't know if ESR1 would ever show up in someone who converted from hormone positive to triple negative. Good question. I will say that sometimes those types of lymph nodes around the chest area are not great at pulling a good, full picture biopsy sample. I was diagnosed with mets via two visible, hard, palpable, large 2cm subclavian lymph nodes which were right below the skin and very easy to biopsy. They were so close to the surface that my surgeon did the biospy with a punch device in his office with local lidocaine and obtained a good-sized sample. That biopsy indicated I changed from my early stage breast biopsy 8 years prior, which was ER+/PR+/HER2-low +2 (technically HER2 negative but considered "equivocal", requiring further testing to confirm HER2 negative status) to becoming ER+/PR-/HER-low +1 (HER2 negative with small amounts of HER2 expression). The loss of PR+ status is a somewhat common, aggressive change to ER+/PR+ BC when the cancer finds it way around hormone therapy by opening up more aggressive pathways and is not known to subsequently close those aggressive pathways and switch back on to being PR+ again once PR+ status is lost. However, all my my later mets biopsies to my liver show me as the same as the early stage biopsy, ER+/PR+/HER2-low +2. My MO and I think the lymph node biopsy was not a representative sample although the sample obtained was quite large and that I likely never lost my PR+. Maybe the cancer cells are too mixed in with the lymph fluid and not as well formed as tumors in other locations? How was your triple negative status confirmed?
You definitely have many attributes on your F1 report that are most often associated with being triple negative. I don't know enough to give more insight. I did an FGFR1 trial of erdafitinib (Balversa) as a monotherapy and it was a total bust with no efficacy for me personally and harsh side effects. There seems to be more luck with efficacy in a trial where erdafiinib is combined with Ibrance and Faslodex but that wouldn't be indicated for you if you are indeed triple negative. There also seems to be some promise in the various trials for ESR1 mutations in hormone therapy resistant BC to resensitize the BC to certain ESR1-targeted hormone therapies, but again if you are triple negative, those would not likely be indicated for you even though you have the mutation. I also have FGFR1, ESR1 and MYC on my F1 report, along with a hand full of other amplifications or mutations. You may want to look into drugs targeting EGFR in addition to the various newer immunotherapies available to triple negative BC or those with sufficient tumor mutational burden. MYC is quite aggressive and I hope that future trials focus more on targeting MYC. Good luck sorting out where to be treated and what to take. Once you have an action plan, you will feel much better!
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JFL- the PA said that if the liver enzymes continue to rise they would probably pause the med (for a week I am guessing) to see if they lower. She also said sometimes a new med can cause a flare and that more time is needed to see if it settles down. If they don’t go down after a week off then they will order a scan. Monday will start week 3 and a ful day of PK blood draw. I get another biopsy at week 6 (they should be able to tell if my reference tumor is growing) and trial scan at week 8.
I am trying to have hope but part of me struggles to believe we found the right “secret sauce”.
Dee
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FYI
The trial below will soon be sponsored at Ohio State. The sponsor is the author to one I have been keeping in my back pocket (NCT04574583). She moved from NIH to Ohio State.
The diagram is very cool https://ccr.cancer.gov/news/article/new-clinical-trial-studies-immunotherapy-combination-for-metastatic-breast-cancer
Dee
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Happy New Year!!!
There are some new reports regarding earlier findings that activating the STING pathway can make immunotherapy work better. Straight up activators of the STING pathway have not worked in phase 1 trials, too many side effects and hard to control STING activity precisely. The new studies show that STING is held back/chewed up by an enzyme ENPP1 and that inhibitors of ENPP1 allow a way to fine-tune STING activity and shrink tumors in mice. There are several of these inhibitors already in development and phase 1 trials are expected this year.
https://www.mskcc.org/news/taking-sting-out-cancer...
https://www.biospace.com/article/releases/mavuphar...https://www.sciencedaily.com/releases/2020/12/2012...
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Happy New Year
Thank you for that link about the STING pathway Cure-ious, that looks very promising!
I managed to speak to my oncologist yesterday and am at a bit of a crossroads. I think I've mentioned before in other threads that there is a question mark over my diagnosis - I have mets to lungs (two nodules) and mediastinal nodes, and they could only safely biopsy the nodes through an EBUS which gets aspirate. That came back inconclusive even for what kind of cancer it is and my team have see-sawed on whether they think it is definitely a recurrence of the BC regardless (in which case it has mutated from ER+ to ER-, stayed Her2-) or a cancer of unknown primary (as officially stated on the biopsy). Last week they were gung-ho that it is indeed BC, this week my oncologist says the breast pathologist has raised a question mark over that again and says she isn't convinced. Meanwhile it's nearly 6 weeks since I was diagnosed...
This back info is relevant because my oncologist wants to put me straight on Gem/Carbo so we are doing something (and she says even if this is not BC gem/carbo works for lung, bladder and ovarian too). I have always said that especially if I converted to TNBC I wanted to do a trial.
The only trial she has suggested is the Keylynk trial combining Keytruda with...gem/carbo. It would involve me travelling 2 hours either way to go to the trial hospital. To my mind I think - why just get the gem/carbo when I could get gem/carbo plus the Keytruda (it is early phase so no placebo)? But my oncologist is nervous saying that especially as I have an unclear biopsy, getting me on that trial will require somehow getting more tissue from my lungs, in the middle of Covid (!) and waiting for results to come back from that, and we could be looking at weeks (she didn't say how many) before I started. And thats if the hospitals here in the UK don't start closing recruitment to trials altogether during the Covid crisis which some are suggesting.
Would you push for the trial, even if it raises all the complications of finding more tissue and waiting for more biospy results and scans and travel? Obviously if I have the gem/carbo straight up I could not do this trial later. But I am also keen to hit this with something - I am sick of the uncertainty and I feel I'm going from asymptomatic to coughing and it scares me.
Thoughts much appreciated!
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Phet...just curious..where are you located???
I personally would do the trial.'
Dee isn't this trial ONLY for HER2+ "
- INCLUSION CRITERIA:
- Patients must have histologically or cytologically confirmed metastatic HER2+ breast cancer. HER2 positive or amplified breast cancer is defined as IHC 3+ or FISH average HER2 copy number greater than or equal to 6 signals per cell or HER2/CEP17 greater than or equal to 2.0. HER2 testing must have been performed in a laboratory accredited by the College of American Pathology (CAP) or another accrediting entity.
- Patients must have hormone receptor negative, HER2+ breast cancer. Hormone receptor negative is defined as estrogen receptor < 10% by IHC and progesterone receptor < 10% by IHC.
- Patients must have measurable disease, per RECIST 1.1.
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Nicole- I’m in the UK, in Oxford. The trial would be London so about a 2 hour drive each way but certainly doable and my partner would be driving me. We have lots of friends in London if we need somewhere to stay overbight
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phet, I was essentially in that position in Feb 2020. There was a trial, but would it shut? I needed further testing for PD-L1 markers to qualify. I needed a whole whack of new scans and tests for applying to the trial and then there was a chance that I would not get in due to some eligibility criteria or that they would shut down. In fact, I got in, got randomized on a Monday and on the Friday our provincial cancer agency stopped enrolling new pts in any trials. Existing pts were fine to continue but if I'd been delayed a bit for a test or something, then that would have been a wasted 4 weeks.
My bigger problem was that I was in visceral crisis. I have liver mets which at that time were causing huge problems. I needed albumin transfusions, repeat blood transfusions etc. I was really not well.
How much are your mets bothering you? Do you have symptoms indicating your lungs are in trouble? Are you ventilating & perfusing well? And do you have a grade on the cell samples - even if they're still unsure of pathology - to serve as a proxy to indicate how aggressive this malignancy is?
If you're fairly stable, I would be inclined to wait a bit, get clear path results and see if you can push into the trial. If you're in oncological visceral crisis, then that would change things. All through my wait period, my MO had the other option on the table - that I start taxol immediately. It would have actually meant being admitted to the cancer ward because inpatients can get chemo immediately, whereas outpatient chemo often takes 1-2 weeks to set up scheduling. So every time I saw her - & it was a lot - the bubble in the room was constantly, do I need to be admitted stat?
Maybe talk to your MO about using visceral crisis as a decision making point? ie "let's try for the trial but if X or Y happens, then immediately start gem/carb"
Covid complicated everything a billion times & I do think you need to take that into account too. With lung involvement,we have to be especially careful so you need to consider that too. You likely wouldn't be able to stay with friends. Your dh will have to self-isolate, work from home, can't go for quick meal while you're getting treatment. My poor dh has been working out of his car in the parking lot of the cancer agency for large chunks of 2020. My MO ordered me into self-isolation & my household into high alert minimal contact. Unless you guys think you'll get a vaccine in the next month or two? I'm not expecting ours for another 6 mos ....
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Nicole , yes the BrEAsT trial is her2 + Er/pr- a very specific group. The other trial at NIH NCT04574583 has a cohort 1 where ER/PR+ can fit.
PHET-
MOTH gave a great summary of decision making criteria. I travel 2 hours for my trial. And it is very manageable, but I don’t work. If I need to be there overnight my study gets me a hotel room(most trials do that). My hubby drives me and uses vacation days(he could work 1/2 days if needed. Every trial is different but many require weekly visits at first for several weeks.PHET, can you qualify for a Transbronchial biopsy or Thoracoscopic biopsy. I realize those are more dangerous but it seems like getting a biopsy would be the most important step to deciding what treatment is best. Many trials require 1 or more biopsies. I asked because that could have been a requirement for me, but I had a liver tumor grow big enough to access with a needle biopsy. Hoping for everything to come to light quickly and you get started on the right treatment!
Dee
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Dee, that is a very exciting trial! Its based on using the vaccine CV301 to activate a cytotoxic T-lymphocyte (CTL) response against CEA- and MUC-1-expressing tumor cells, which are found in a variety of cancers. It also upregulates PD-L1 expression and therefore is tested in combination with a PD-1 immune checkpoint inhibitor, The third component in this trial is a CXCR1/2 inhibitor, which is hoped to better expose the tumor to the immune system, and may also have some anti-angiogenic effects directly on the tumor.
So thanks for the tip, Dee- got any other trials in your back pocket?!
In addition to the above trial, the CXCR4 inhibitor Balixafortide is currently in phase 3 trials with Halaven, with results expected to report out in this spring and then the overall PFS report would be this fall. Preliminary results indicate it may double the effectiveness of Halaven. If their results remain strong, the combo could be eligible for expedited FDA approved as early as a year from now, or otherwise they could get regular FDA approval in first quarter of 2023.
It would be good to see more :"chemo boosters".
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