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Progression after ribociclib (csk4/6i) and letrozole

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Hi

I had her2 neg er+ breast cancer in 2018.

In 2022 i had recurrence in my bones (all over with 3 collapsed vertebrae) and liver.

I was on ribociclib and letrozole that worked really well, pet was negative and most metastasis disappear.

In August I had liver recurrence.

Blood test and markers are ok and i feel well so i didn't expect it at all! I'm so scared!

I had 3 different opinion for 2L terapy: capecitabine, or docetaxel, or eve+exe.

What did they suggest to you after ribociclub or other cdk4/6i?

I'm on italy and it feel so behind here compared to USA oncology...so I want to ear your oncologist opinion as well!

Also do you know where I can get a free online second opinion in USA if I'm not from there? (My husband is from San Francisco but now is many years he live in Italy with me and our 3 year old kid so he have no longer medical insurance).

Thank you!!

Comments

  • cure-ious
    cure-ious Member Posts: 2,756
    edited September 2023
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    Hi Amel, I'm so sorry you are dealing with this so young, and at such a wonderful time of raising a toddler!! I wonder if you have gotten some blood test (or even a new biopsy), such as Guardant 360? I think this is especially important after progression on firstline, its important to try to learn why the cancer was able to escape from Ribociclib and Letrozole. One of the most common mutations would be ESR1, which is where the estrogen receptor has mutated so that it drives the cancer growth, but in a way where it does not depend on estrogen. This used to be a scary mutation, but nowadays its kind of good news, in the sense that it means that the cancer remains very dependent on estrogen receptor, and so would not be a reason to go already to chemotherapy, but instead to move to Faslodex or even better, a SERD like Elascestrant (depending on what is available there). If there is an ESR1 Y537S mutation, then that is also resistant to Faslodex, and you would want a SERD, which you should be able to get in a clinical trial there. And, if the testing does not show CDK2, Rb or CCNE changes, or an increased tumor mutation burden (TMB), then there is no reason to think it is resistant to a CDK4,6i. So in principle a SERD with a different CDK4,6i (like Ibrance) would be I think the most common choice here, and in Italy it would probably be accessed through clinical trial. In general, the trend is to try to put off chemotherapy as long as possible and work with the newer hormone therapies. If it were me, I would not want everolimus & exemestane because I would be concerned those aren't strong enough. If the testing showed a PI3KCA mutation, then perhaps faslodex with everolimus would be good. There is no reason to automatically dump the CDK4,6 when most of the time it is just the endocrine partner that is failing…

  • amel_83
    amel_83 Member Posts: 157
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    Hi, i did a liquid biopsy, and i'm waiting for the results on the 13. I just feel like in a hurry to start a cure...

    I will ask if they test for ESR as well, thank you very much for the important info!!

  • amel_83
    amel_83 Member Posts: 157
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    Hi, can I ask you one other question, if you know?

    And what if any of those medicines are good for me because I do not have the ESR mutation or I have a change in CDK or other...and I will have to choose between docetaxel or capecitabine...i don't know if it is better a more aggressive approach, that may work better, or a less toxic one (ribociclib and letrozole were my very fist line of treatment). What you think most oncologist will suggest there? Knowing I have a relapse in the liver(pretty scarry!!) with two 5 cm tumors, happened in about 6/7 month. With a well functioning liver. And no relapse in bones.

    Also wat if I start for example capecitabina, just because it is a month that I'm not taking any medicine (I'm so scared of stay without taking anything!), and than when I find out my results and than may look for a clinical trial, and see i'm a candidate for a different medicine, can I just switch like that, after only 3 weeks? Or it is better to finish the line?

    (I know it take at list 2 weeks for enrolling a trial plus a week for my results...so i don't want to wait 3 more weeks, especially not been sure i can even take a different medicine or be insert in a trial...)

    Also I have a score of 10000 for TYMP protein, the one that may be connected on how capecitabine work, they told me it is one of the higher score ever recorded...do you know if it really matter? It seem that the oncologist I tolk with had a very different opinion on it.

    Thank you, and sorry for the too many questions!!


  • cure-ious
    cure-ious Member Posts: 2,756
    edited September 2023
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    Amel, It looks like the report has some actionable items. RET is a growth factor (like Her2) and is associated with resistance to AIs, and the FDA approved the use of selpercatinib for any cancer with RET expression, fusion, or mutation, so you may be able to access this drug? Also there are some next-gen RET inhibitors that may be more specific and/or last longer, described below. And would be good if these could be combined with endocrine therapy, its worth asking if that is possible. PDL1 expression suggests immunotherapy combination trials might be good also- there is a trial of Xeloda with immunotherapy for ER-positive breast cancers, among others. And of course Trodelvy is an ADC and there is a thread here about it. It sounds like you might also benefit from a second opinion, for example someone at a major cancer center with breast cancer trials, for future treatments. Good Luck!!

    https://www.mdanderson.org/cancerwise/ret-inhibitors--a-treatment-for-any-ret-altered-cancer.h00-159544479.html

    https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1090757/full

  • amel_83
    amel_83 Member Posts: 157
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    Thank you very much! You are so aknledge!! I will check out everything and show it to my oncologist and look for a some other second opinion as well

  • amel_83
    amel_83 Member Posts: 157
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    Sorry i read and read you post, and I'm wondering...what does it mean in practical that "RET is associated with resistance to AIs"? Does it mean it is resistant to some kind of medicine?

    i can't find the info online, and I have an appointment with an oncologist/researcher this evening I want to talk about it with him.

    Thank you for all the info!

  • exbrnxgrl
    exbrnxgrl Member Posts: 4,950
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    AI’s , aromatase inhibitors, are a class of drugs most often given to post-menopausal women whose breast cancers are estrogen positive. This group includes letrozole, anastrozole, and Exemestane. The y are also sometimes used with pre-menopausal women who are taking ovarian suppression drugs as well.

  • anx789
    anx789 Member Posts: 238
    edited September 2023
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    Hi, me too is taking Kisqali with Faslodex, since 10/2022. Current Petscan shows progression and new lesions on same body parts (bone only). I have extensive bone met and lung nodules. Liver and kidneys are clear; lung nodules are stable. Is this considered a progression? MO wants to change treatment, im scared. Any advice will be appreciated.

  • amel_83
    amel_83 Member Posts: 157
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    @anx789 sorry to ear that, but at least the other metastasis are not moving, that's very important, and the bones one are less dangerous in comparision...I hope they will find the right medicine, let me know what they told you to do! For me they end up choosing capecitabine because of liver metastasis (capecitabineis processed in the liver), and they found a really high level of a protein in my biopsy that answer well to capecitabine...and no other mutation come out in my recent liquid biopsy unfortunately...

    Anyways good luck to both of us!

  • anx789
    anx789 Member Posts: 238
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    @amel_83 Yes, good luck to us! My MO will test for mutation before deciding the next step and I think she said if there is no mutation found, another CDK4/6i is an option. I will keep you updated.

  • anx789
    anx789 Member Posts: 238
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    @amel_83 just an update, i saw my second opinion doctor from City of Hope California, he recommended to do a biopsy to see if im still estrogen positive. If positive, next will be Afinitor or Piqray; if negative, I’ll do Xeloda. He didn’t recommend another CDK4/6 as a second line of defense.

    Fyi, my main MO recommended Abraxane as first line of defense but I opted for Kisqali. Now I’m leaning towards Afinitor against Piqray, because I read Piqray is a little tough. Hang in there..

  • amel_83
    amel_83 Member Posts: 157
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    @anx789

    Thank you for your answer, I will check those out too for the future.

    Best wishes!