Are you currently (or have you been) in a Clinical Trial?
Comments
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Another trial that is farther off but worth watching for is the engineered IL18 cytokine that will be run out of Simcha therapeutics- it was just published last Dec in Nature, but they say they have the financing to test it with immunotherapy, plan to file an IND early next year and hope to have a trial in solid tumors starting in the first half of next year. so not here now, but coming, and that really could make IO work..
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Abemaciclib/Tamoxifen Shows OS Benefit in HR+, HER2- Metastatic Breast Cancer
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more on those Troveldy overall survival numbers:
https://www.onclive.com/view/sacituzumab-govitecan...
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Thanks for posting the new Verzenio-Tamoxifen data, 42Young!! Presented by Erika Hamilton, Dee's MO!
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I read the paper that Cure-ious sent about the 10 genome-driven classifications. We already knew that the old stage I-III classifications were meaningless. The genomic-driven classifications make so much more sense. Has anyone done the testing necessary to discern their genome-driven classfication? The other eye-opening discovery was how many of the classifications (4,7 and 8) had very high 10-year survival rates of 80%.
MargaritaMS, I loved that you referred to me as "our own Susan in SF"! Brought tears to my eyes. This such an awesome community of supportive and knowledgeable women!
Hugs, Susan
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Susan, I too have gone back to re-read that 10 classifications article. I was struck by some tnbc being in (I think) group 4 ... one of the ones with the longer OS prognosis. That is unexpected!
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Hey y'all
With this talk about genomic driven classifications it reminded me about a question. Does anyone have any suggestions for which company NGS to use at this step?
So I am getting a biopsy with my clinical trial and they said I can ask for extra punches to get another NGS. My first one was done at MDACC. This one will be sent off.
Sarah Cannon trial intake Nurse said it will be up to Dr Hamilton. But I think I should at least be able to talk intelligently about it.
I am following the author of this article -she used to be at NIH and now she is at Ohio State.
In recent years, requesting oncogene panels (e.g., FoundationOne, Oncomine, CANCERPLEX, Caris Molecular Intelligence, Tempus, MSK-IMPACT, and OmniSeq) has become standard of care in many oncologic settings. However, despite the wide use of these panels in clinical practice, professional guidance on how to interpret and apply the findings of the oncogene panels for individual patients is lacking.
"Future research will focus on exploiting these known genomic alterations through the generation of new therapies and/or with the identification of the optimal sequencing of agents."
https://www.medpagetoday.com/reading-room/asco/breast-cancer/88621
Any thoughts about which company to research to be able to talk about? I am a little familiar with Foundation one but none of the others.
TIA
DEE
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Dee,
I have done both UCSF500 and Foundation One. Foundation One gives you a much longer report (20 pages) but most of it is standard information you can find online about each mutation that shows up. The UCSF500 report was concise and more quantitative. Neither gave me any information on gene expression levels such as Ki67, PD-1 (I had a separate test for this done and it came back negative), Aurora A kinase or comparative genome hybridisation. Would love to find out which of the ten integrative cluster I fall but don't have the info to do it.
Hugs, Susan
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Dee,
The article was really interesting -- thanks for posting the link.
I can't advise you, but I've had Foundation One tumor testing as well as blood testing. The ones I've seen the most frequently on these boards, in addition to F1, are Caris and Tempus. Hopefully others will weigh in.
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Ive had F1...but I am next time going with Tempus..that is who my cancer center is now moved to and my MO mentioned that it does more than F1..I can't remember exactly what she said but she said she prefers it now...and I know she wasn't JUST saying that bc they use it bc she offered to do F1 if that is what I wanted.
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Regarding the ten METABRIC classifications — First, am I right in thinking that these are based on a prospective study of early stage breast cancers? In this case, how useful or not are they for recurrent breast cancers or de novo stage iv? I have racked up additional mutations over the years; do I apply those now?
Second, I read this paper years ago, but like Susan, I did not have the info needed to choose a cluster. My first F1 report in 2014 showed only three deleterious alterations and nine VUS. The F1 only looked at maybe five somatic mutations noted in my candidate clusters, those candidates being #2, #3, and #8 because of CDH1. So ultimately I cannot say which cluster since only CDH1 matches. Obviously this cancer carried a poor prognosis for me, since it recurred after only three years.
Has this gone anywhere? Is anyone actually using it to help determine early stage treatment? Stage iv treatment? Frustrated because it seems so brilliant but I don't see how to apply it.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3590990/
(2013).
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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4603750/
Similarly, Comprehensive Molecular Portraits of ILC ( 2015)describes three subtypes of ILC: proliferative, reactive-like, and immune-related. But the paper is so dense and technical that I have not been able to figure out which type to choose, and how it relates to METABRIC. I feel there may be something of importance here but... If I had known, I would have majored in cell biology.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4700448/
Integration of genomic, transcript is and proteomic data identifies two biologically distinct subtypes of invasive lobular breast cancer (2016)
The two types are immune-related and hormone-related. This paper is not quite as difficult and it seems if we could apply it, it might help us ILC patients to think about how interested to be in immunotherapy based on our ILC subtype.
Bev, have you discussed either of these with your oncs? I haven’t in recent memory.
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Good questions, all, of course the classification itself is informative especially as several of them are based on an amplification of a particular part of the genome, that seems very relevant; I did not realize MBC had these different amplifications, other than the HER2 one. And now we have a direct hit in terms of "usefulness", because those in IntClust1 with 17q23 amplification can be effectively treated with a PLK4 inhibitor. Ideally, we would know from the genomics report which cluster we are in and the best treatments and sequence for each group, providing some kind of framework that can be built on as more trials go on. But nobody seems to be collecting the clinical trials outcomes data this way. Well, at least they do look for biomarkers, and I guess eventually the mechanism becomes clearer
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Dear All, what an interesting discussion. I think we are coming to a phase, where RADIOLOGICAL staging I-IV becomes meaningless, as stage I-III is basically just prediction with probability that they are not stage IV. No one knows if at least few cells have escaped primary tumor and is lurking somewhere as micrometastasis for years, sometimes even 20 or more. Therefore right attitude would be to shift diagnosis to genomic alterations and consider any cancer as potential "stage IV", then move on to making stage IV a chronic disease, then move on to the cure. There's no other way. Saulius
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SP,
I am having the same issue as you with the classifications in the first articles. Like you, I have the CDH1 mutation. But I also supposedly have 24 more, and I can't seem to fit myself in there.
I'll have to review the article you posted about ILC. No, my oncologists have not discussed the lobular stuff, except to say "we know your cancer is slow growing." Not exactly a revelation.
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I wanted to post this inspiring graph again showing the huge benefit of the anti-Trop2 ADC Trodelvy for TNBC PFS. On Twitter, oncologist Fabrice Andre was commenting that they cannot wait for a trial that will test this drug in combination with Ketyruda/immunotherapy, what if they synergize?! He says with what they know about TNBC biology, this combination could completely transform treatment of these cancers..
Well, this is why Gilead (with their own immunotherapy) bought Troveldy maker Immunomedics for 21B. They think/hope the combo is going to be a game-changer
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I don't think we really discussed the trial for Enhertu. That is the antibody drug conjugate that uses Her2 antibody, and is designed for cancers that express even low Her2 protein levels, without the gene amplification that gives really high Her2-positive cancers. Among the ER-positive breast cancer group, about 60% are Her2-low, and about a third of TNBC is also Her2-low.
What I didn't realize is that the Enhertu is in phase 3, with 200 locations-its all over the US, Europe, China, Japan, Korea, Canada, etc. The trial is scheduled to finish in 2023. Here is a link:
https://clinicaltrials.gov/ct2/show/NCT03734029
Requirements for the trial are not very restrictive- patients have low levels of Her2 expression, are no longer sensitive to endocrine therapy, and have had 1-2 chemos in the metastatic setting. They cannot have been treated with prior ant-Her2 drugs, never were diagnosed as Her2-positive, and have to remain eligible for at least one of the chemos on their list of physician's choice (ie, the control group).
Here are the results of phase 2. Note that because some people have Her2 expression in normal cells in the lung,there can be a pneumonitis that develops, they have to watch carefully for that.
Results
Overall, 184 patients who had undergone a median of six previous treatments received the recommended dose of trastuzumab deruxtecan (5.4 mg per kilogram of body weight). In the intention-to-treat analysis, a response to therapy was reported in 112 patients (60.9%; 95% confidence interval [CI], 53.4 to 68.0). The median duration of follow-up was 11.1 months (range, 0.7 to 19.9). The median response duration was 14.8 months (95% CI, 13.8 to 16.9), and the median duration of progression-free survival was 16.4 months (95% CI, 12.7 to not reached). During the study, the most common adverse events of grade 3 or higher were a decreased neutrophil count (in 20.7% of the patients), anemia (in 8.7%), and nausea (in 7.6%). On independent adjudication, the trial drug was associated with interstitial lung disease in 13.6% of the patients (grade 1 or 2, 10.9%; grade 3 or 4, 0.5%; and grade 5, 2.2%).
Conclusions
Trastuzumab deruxtecan showed durable antitumor activity in a pretreated patient population with HER2-positive metastatic breast cancer. In addition to nausea and myelosuppression, interstitial lung disease was observed in a subgroup of patients and requires attention to pulmonary symptoms and careful monitoring.
https://www.nejm.org/doi/full/10.1056/nejmoa191451...0 -
Dear Cureious, as far as I follow, Trodelvy and Enhertu are really game changers. There are a few others that are Her2/Her3 (like Merus MCLA-128, Daiichi Sankyo U3-1402) or bi-specific (like Genentech/Roche BTRC4017A, DragonFly DF1001, Bolt BDC1001, Novartis NJH395). So lot's of going on in Her2, Her3, Her2low and TNBC space. I have a feeling first "cures" might come with combinations of one of these and some IO drug like Pembrolizumab or Atezolizumab for Her2/TNBC and one of these plus CDK4/6 for HR+... let's not forget Leronlimab for TNBC too (https://apnews.com/Globe Newswire/0e3d6eb4070641fd556d4b5a193eb9f2). I think finally big-pharma is onto stage IV... let's hope we can still taste the fruits of these efforts. Saulius
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Saulius, There are also various approaches to get solid tumors to open up to immune cell killing that could also contribute, but getting what is basically a targeted chemo to do a PFS of 16 months, on patients who have been already extensively treated, is really impressive. I'm not sure it would help to combine with I/F, since endocrine therapies slow down cell growth and put cells to sleep, whereas chemo agents tend to be designed to kill cells that are rapidly dividing? But pre-clinical studies can direct them which direction to go, and with numbers like these we will be seeing more FDA approvals and more combo trials come up!
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Anyone with a ATM inversion exon55 gene mutation tried a PARP inhibitor? My F1 report suggested that.
The 2020 bx came from my liver.
Also my original 2016 liver bx mentioned Her2-, but 1+ IHC. Would I be eligible for Enhertu?
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Sandi what is IHC?
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Some labs use either FSH or IHC (immumohistochemical) for evaluating HER2. Think I got that right..
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Thanks Sandi
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Stable scans on Monday so will be able to stay on Trodelvy until my next scan in six weeks! One of my tiny brain mets disappeared. Probably not due to Trodelvy because I haven't heard that it passes through the blood-brain barrier.
Searched for the clinical trial of Daiichi Sankyo U3-1402 but couldn't find anything but news releases. Does anyone have more info? I am ERBB3 positive but looks like you also have to express PD-1?
Hugs, Susan
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Dear Susan, they have open clinical trials for NSCLC and colorectal disease with U3-1402, NCT02980341 for MBC is not recruiting anymore but it would be good to write them, as other arms/phases might open up. U3-1402 (Daiichi Sankiyo code DS1602) is a direct Trodelvy competitor but has another payload, same as Enhertu does, therefore should work even if resistance to Trodelvy was acquired (same happens with Kadcyla vs Enhertu). Saulius
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If we are Her2- how low of expression to do we have to have to get Enhertu?? How do we see the "amount" of expression we have of Her2 on our F1??
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Dear Nicole, IHC or FISH should tell... for Sandra it is IHC reaction HER2+++ 100 % of tumor cell membranes. One lady showed me her report at NCI and it stated Her2+, 10 % of tumor cell membranes. Check for your initial biopsy maybe...
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well I’m in limbo land right now.
Disqualified from the Op 1250 CERAN study due to hypogammaglobulenemia diagnosis 😢 it took the Sarah Cannon trial intake nurse 10 days to call the pharm company to verify at my insistence. 1 day to get an answer.
Back to the CDK 2/4/6 trial. I am told I am on the list and just waiting for Pfizer to give the go ahead to sign consent. Could take 2 weeks. 🥴
Meanwhile I am washing out and not on any cancer treatments. 😳 Scarry
Good news is my bloodwork is great accept for IgG which keeps going down. My local MO said if it drops below 700 we will have to start IVIG back up. He said to give the trial 2 weeks to start up or I will go back to standard of care. Probably gemcitibine/cisplatin since I have not had a platinum drug and that would be good to see if I respond for the Neuroendocrine component.
I need to vent-😤
I do my own research for myself.
I found the cdk 2/4/6 trial here.
I had to ask MDACC if they would offer it to me.
I reached out to Sarah Cannon on my own since they are closer.
I got MDACC to call Pfizer to get the OK for IVIG.
I got Sarah Cannon to reconsider me as a patient because of the IVIG and ok from Pfizer.
I said ok to Dr Hamilton to look for other trials to be sure I get the right one.
I got disappointed because the door closed on serds/serms/ceran trials even though I have ERSR1 mutation.
I am anxious about the wait and the not being on treatment.
I feel so out of control.
I have not told my kids and extended family yet because I don’t want them to feel my pain and frustration.I am having second thoughts about doing a trial when it’s this hard to get into one and it may not be the best next step.
I AM TIRED OF CANCER DOMINATING MY LIFE!
I am thankful for this group. 😘
Dee
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Oh, Dee, I can feel your frustration coming through your message -- and rightfully so. Your story is one of persistence, and even with the door closing on the trial you were trying to get on, your persistence will continue to lead you down the right path.
You have the right to vent -- so vent away! No one understands like us MBCers, that's for sure.
Is there anyone who could get Pfizer to move more quickly on the CDK 2/4/6 trial? You are your own best advocate, but I'm sure that it's difficult to cut through the administrative BS to find the right person to talk to.
Fingers crossed for a solution to this issue or-- if you go on the standard of care treatment -- for that to work well for you.
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Dee, Nothing but admiration and support for you!! It is ridiculous what you are going through and have had to do on your own. Hopefully you will work your way out of this maze to a safe place, but there are no excuses for everything you've had to go through, the cracks in our system are just enormous.
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