ARV-471?
I have been suggested for a clinical trial using ARV-471 to treat early stage HR+, Her2- breast cancer. I was wondering if anyone has any experience with this drug. It's typically used for metastasis but I want to respect their boards and not post there. Thanks to anytime who has any feedback!
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Hi @cmre00! We had to look up the details on this and indeed, it is typically use for metastatic.
Have they explained why they are suggesting this trial for you?A second opinion on whether this trial is good step for you may be helpful at this juncture.
Would love to hear from others.
What stage exactly was/is the cancer? We know you said "early stage" but not sure exactly which one.
This is one thing we found on the trial:The purpose of this study is to learn about the safety and effects of the study medicine ARV-471 (PF-07850327, vepdegestrant) compared to fulvestrant (FUL) in participants with advanced breast cancer. Advanced breast cancer is difficult to cure or control with treatment. The cancer may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body, i.e. bones, lungs, brain, or liver. FUL is a medicine already used for treatment of breast cancer while ARV-471 is a new medicine.
This study is seeking participants with breast cancer who:
- have cancer that has come back in the place where it started or spread to nearby tissue, lymph nodes, or distant parts of the body.
- cannot be fully cured by surgery or radiation therapy. Radiation therapy is the use of high-energy radiation such as x-rays, gamma rays and other sources to kill cancer cells and shrink tumors.
- respond to hormonal or endocrine therapy (which target hormones and/or activity of hormone receptors) such as tamoxifen or aromatase inhibitors (this is called estrogen receptor positive disease)
- have received one line of CDK4/6 inhibitor therapy (for example palbociclib, ribociclib or abemaciclib) in combination with endocrine therapy (for example letrozole) for advanced cancer.
- are allowed up to one other endocrine therapy (for example exemestane) for advanced cancer.
Half of the participants will be given ARV-471 while the other half of the participants will be given FUL.
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Thank you for responding. I am Stage 2A. They are testing this drug in newly diagnosed, HR+ Her2- people who have a >=2.5cm tumor and mammaprint unlikely to respond to chemo. They want to see if it works well in these situations. I did get a second opinion and they feel the trial is not in my best interest. They said that endocrine therapy in the neoadjuvent setting looks promising and may be in years to come but since I have a positive lymph node they think I need surgery first, then rads and endocrine therapy. Typically neoadjuvent endocrine therapy takes 6-9 months to see improvement (the trial is for 6 months). My second opinion feels that I shouldn't do that. I think the trial is pretty new and I've been unable to find anyone else who knows much about it. I was hoping someone here might know more. Here is a link:
https://www.arvinas.com/press-releases/arvinas-and-quantum-leap-healthcare-announce-clinical-study-to-evaluate-vepdegestrant-arv-471-in-i-spy-2-endocrine-optimization-platform-eop-clinical-trial/
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Hi @cmre00 , Are you referring to the I-SPY 2 trial NCT01042379? It is an neoadjuvant adaptive trial for stage 2/3 cancer with high risk factors. There seem to be many different drugs being tested including ARV-471. The treatment you receive depends on biomarkers found in their analysis of your tumor. I have no personal knowledge of this trial but there is a paper which explains how it works. Some drugs seem to be successful while others are not. Here is a reference to the paper. Hope this helps.
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@maggie15 Hi! Yes it is a part of the I-Spy trial. It is a special arm of the trial called Endocrine Optimization Pilot or Protocol (something like that). There are a few different arms of the EOP study that I could go into with different drugs. Arv-471 is in three of those arms. I would be randomized into them. In the main study if you respond to treatment quickly you could go into surgery quicker but this one seems to be a set 6 months. Obviously I could leave it if I chose to and the doctor could take me off of they felt they need to. I still have a lot of questions but honestly I don't feel like the MO is keen on going over it again. She met with me about it before but that was before we knew that I was going to be out into EOP. And she couldn't answer all of my questions anyway. This process is so hard!
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I was in a similar situation to you (3.2 cm tumor, one positive node, Oncotype 24 so no chemo recommended.) I’m not sure that I would have wanted to wait six months for surgery and radiation. There may be some benefit in reducing the risk of future recurrence (I had LVI so I’m at higher risk for that) but nobody knows. I guess that is the point of the trial. You just have to decide which course of action you are more comfortable with.
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I am definitely feeling that way. It's a long time to wait and see if something is working. For this arm they do biopsy and MRI at 3 weeks, 12 weeks and 24 weeks. That's a long time in between MRIs to be waiting to see if it's working.
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cmre00- Can't your oncologist just give you some neo-adjuvant AI +CDK4,6i for a month or so if they want to shrink the tumor before surgery? There are many good options. And then you continue on with that post-surgery? Not sure how you came to be in this trial?
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Ugh. I wrote a long response and then accidentally cleared it.
My MO who recommended the trial hasn't given me any other options. The SO said they were recommending neo-adjuvant chemo (before my Her2 and mammaprint came in). When the MO came in she mostly talked about the trial. I did agree to be screened. But they didn't tell me about the EOP study at that time. That came later.
When my node came back positive and my her2- I asked to meet with the MO again. I had gotten a second opinion from another MO who said she felt like I needed surgery then TC chemo. She quoted a study released in Feb 2024 that said TC chemo overall had statistically the same benefit as ACT due to the ACT side effects. So I went back and asked the first MO about that and she said she wasn't familiar with that study and that she didn't think that was a good idea and she again recommended this trial. She thinks it could save me from having ACT.
So then I met with another surgeon who said she didn't think the trial was in my best interest and she thinks I need surgery ASAP but she can't do it till Sept 30th! She said the other SO I saw is very good so I could do the surgery there but not do the trial.
So I'm trying to find out when the SO at the first hospital can do the surgery. I also have a meeting Wednesday with a third surgeon.
It's been 5 weeks since I was first diagnosed. And weeks before that that I was trying to get help because I was originally told from my mammogram that I didn't have cancer. This whole ordeal has been a nightmare!
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This is the study the second MO quoted.
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cmre00.
This was for your best interested so you understood, but the varying Doctor suggestions are making me question what is going on. I would like to think based on your Stage/Grade. ER/PR+/HER2- that there is a treatment plan in place for these statistics. A genetic marker could skew it.
What surgery are they doing?
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I feel like there should be a treatment plan too but I just feel like I can't get a straight answer. Which is why I'm trying a third hospital! The hospital pushing the trial is an NCI rated hospital but I feel like I barely get any contact there. I called the nurse navigator today to ask about surgery and she said she'd get back to me before the end of the day but she didn't.
The surgery would be a BMX. Because there are two tumors they are recommending against breast conservation which is fine because that's what I wanted anyway.
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I am at City of Hope in Duarte Ca. Since they are research driven, I had Stage 2 and all that with Brca 2 tossed in and their " MO team" met to discuss the best treatment for me. My MO gave me Lynparza after i ended up with pancytopenia after 13 rounds of chemo. It is usually used for Metastatic patients.
It is crazy no one returns calls. I would give the nurse navigator one more try. Pick the place that looks at your results and says i have a plan that has had good results with a lot of women.
Our bodies. I am 1.5 years since my BMX and I am grateful to have had the medical team i had. If i did not hear from the Doctor, i got the NP.
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Hi @cmre00,
Do you know how large your primary tumor is estimated to be, based on scans and / or biopsy reports? Patients with large tumors (5cm and above) usually receive neoadjuvant chemo to try to shrink the tumor size and improve surgical outcome, particularly if your team is leaning toward breast-conserving surgery. If your team suspects that neoadjuvant chemo alone will not be as effective (based on your low Mammaprint results), this may be the reason they are recommending this clinical trial, in which the ARV-471 would be used at the same time as neoadjuvant chemo).
If your primary tumor is estimated to be well below 5cm in size, then this may be the reason why your second opinion disagrees with your first oncologist's treatment plan.
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Hi mod. Thank you. My primary tumor is estimated to be 2.8cm. They said breast conservation surgery is not recommended since it's in 2 places in my breast. I wanted a BMX anyway.
The arv-471 would be in place of neo-adjuvant chemo. After 6 months on the trial I would proceed to surgery and then my team would decide what to do from there. They assured me I would not progress on the trial, it would either improve or stay the same. I'm not sure how they could guarantee that though.
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From what I read in the paper I referred to this trial takes those with tumors >2.5 cm and started in 2010. It seems to be a very efficient way of deciding which drugs under development are worth using in phase 3 clinical trials. As of the date of the paper (Dec 2019) the pCR rate in the experimental arm was 35%, not exactly awesome. They claim that the MRI monitoring they do prevents patients from progressing but there seem to be just 3 scans done over six months. Taking part in this trial probably helps in the development of effective drugs but might not provide optimal treatment for the participants. I suppose those who participate find out how well they respond to their drug. This is probably why your second opinion onc didn’t recommend it.
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@maggie15 Yes that sounds about right. They are frequently moving drug and and out of the trials so things progress faster. Overall I think the I-Spy method seems to be good. In the other arms they do more testing and monitoring but because this is endocrine therapy and it's slow moving they don't monitor quite as closely. Being neo-adjuvant that's concerning to me. I did not see that 35% PCR rate. Would you mind linking the article? Or PM it to me please? Thanks!
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Hi @cmre00 , The article reference is at the end of my first post on 8/18 but I couldn’t get it to link live (blue) using my tablet. The drug companies have used similar techniques to sort out the most promising treatments for Alzheimer’s and melanoma. The Bayesian statistical techniques used are cutting edge so the design is good. Also, it’s possible that one of those drugs might lead to a reduced risk of recurrence. I’m not sure how much of a personal risk it’s worth to deviate from standard of care when you are stage 2. Those who take similar risks at stage 4 are in a different situation.
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@cmre00 - My two cents worth is that any oncologist who seems to be pushing you into any trial - especially when others are not recommending it - and whom you feel is not answering all your questions is not someone you should be getting care from.
Yes, it could be beneficial, but it is a trial. It is fine to offer it to you, but in the end it is your choice, not hers. And she should support a well-researched and proven option if that's what you want.
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@ratherbesailing Thank you! That is a very good point and something I have been thinking about as well.
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I must say mine was 5cm, and fast growing. That is why i had the neo-adjuvant to shrink the tumor for better margins. 13rounds of chemo of3 types and it shrunk 1/2, barely. Because of covid, my surgery was moved back 1 month. In 2 months, it was growing again. The team needs to fit the treatment to your results. I was stage 2 as well. My oncologist talked roundtable with other oncologists. For me, I got Herceptin/Perjeta infusions 18 times every 3 weeks. I got treatments proven to help in metastatic cases.
As to research studies, I was offered one this past April to prevent GVHD for my bone marrow transplant. Others had done the early stages of using this drug. I was one of 20 at COH using it for 60 or 90 days. I got it 90 days. So far at 134 days after transplant, no GVHD. YOU MAKE the choice. My DR. did not insist i join the research study. He gave me the information, explained it and let me make the choice. I had real results I could see as a possibility. What would yours be? Those cancers cells and tumor are not our friends.
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