What Treatment Options Can I Consider Next?

DivineMrsM

What’s next for treatment for me? In 2011 I was dx mets to the bone and had chemo, lumpectomy and radiation. Then I was on Arimidex for about 7 1/2 years.

This March, I had progression to numerous bones for the first time since 2011. So I was put on Aromasin and Ibrance, After four months, my September scans showed more progression to more bones. Onc kept me on Aromasin and put me on Verzenio.

I’m in my 4 th month of this combo and I don’t feel any improvement.I have some aches that seem to stick around whereas before, Arthritis strength Tylenol took care of most of it.

My onc apt isnt until Feb but I don’t see myself being able to wait that long. I am pretty sure scans will show more progression.

What’s next? Do I have to stay on a CDK inhibitor? It is really messing with my QOL not to mention not keeping the cancer from progressing.

I think I will call the onc soon and see if I can get scans, but I’d like to have some idea of what treatment options would be available to me now. Any advice is appreciated.

Cure-ious

Eight-plus years on anti-estrogens, Huzzah!!! Hopefully you will be a super-responder to all the drugs!

Standard of care is probably Xeloda (oral chemo) or Halaven, but without liver mets (and therefore no new biopsy) its hard to know what targeted drugs would be suggested.

Blood test can determine if there is a PI3K mutation, in which case Piqray and anti-estrogens would be a good way to go. Have to pre-treat for rash and watch the blood sugars, but this would restore estrogen sensitivity to the cancer.

Not sure how they measure for ESR1 (estrogen receptor) mutation, which is a common route to progression, but the new SERDs in clinical trials are very good for that.

CDK2,4,6 inhibitors and Crizotinib (MET inhibitor) are in trials, and for that matter combination therapies that include Xeloda are in trials.

Not sure if they can test for FGFR1 amplification, but if it were high you should respond to Aromasin-Affinitor (OTOH, if it were high you would not probably have done so well with the anti-estrogens)

We all will be following closely to see what you choose!!

Piggy99

Divine, I'm so sorry you're in pain and that the meds might not be working (although I seem to remember that some ladies like Candy had increasing pain but no progression). I'm not a doctor, but it's possible that unless there's an explosive increase in mets your onc might want to give Faslodex a try - seems to work fairly frequently even when aromatase inhibitors don't. You'll probably have the option of taking it on its own or adding it to Verzenio. I know you're worried about the QoL on Verzenio, but maybe a lower dose would have fewer side effects and still help "prop up" the faslodex?

Your doctor could also run a genomic test and see if you have the mutation that would qualify you for Piqray - it had pretty decent results, but it does seem to be hard to tolerate by some people.

Xeloda would be another oral option, and then the rest is iv chemos that I don't know enough about to have an opinion.

Now, if I were in your shoes, and I realize that I'm not, I would probably look into an oral SERD trial. SERD's are "cousins" of faslodex, except that the new ones are oral, instead of injectable, and seem to work better than faslodex on ESR1-mutated cancers. It's possible that after all this time on aromatase inhibitors at least some of your tumors have developed ESR1 mutations.

I think the most advanced SERD is elacestrant, and there is a site recruiting in Cleveland (for some reason I think you're located around there). My doctor is excited about the oral SERDs, and if you don't get into the active arm you're still probably going to be on faslodex, which would be a good choice as well.

These are just a couple of ideas to think about - the scans and your tolerance for travel, hassle, side effects, non-oral medicines and so on would likely play a big part in the final decision.

Best of luck, and fingers crossed that the pain is bone rebuilding, not progression.

pajim

Hi DivineMrsM, to me you have three [reasonable] choices. There may be more and my choices are also listed above by others.

(1) Faslodex. Maybe in combination with letrozole (yes I know you took it for a while)

(2) Piqray & Faslodex if you have the mutation. I'm starting that now even though I've taken Faslodex for a total of 4 years previously. Odds this works are iffy but for you it's different. You're not pre-treated with Faslodex.

(3) Xeloda

All are pills and/or shots. My goal was to stave off i.v. chemo for as long as possible. Your feelings may vary. If so you can consider Taxol, or Halaven (equivalent) or Navelbine which it what my onc would have given me if for some reason I couldn't have "hard-core" chemo.

I'm sorry you're in pain. That really sucks. Try ibuprofen or naproxen if Tylenol isn't doing it? Just make sure you take antacids and food.

DivineMrsM

Piggy and Pajim, thank you both for your compassion and your detailed replies. I want to have an idea what my options will be the next time I see the onc. I really had no knowledge what different treatments were available, so I appreciate all the information. Thanks, Piggy, for also mentioning a trial that might have some hope for me. Interesting to note Candy had increased pain but not progression. Pajim, I’m allergic to ibuprofen and naproxene sodium, so only tylenol for me.

It seems like I have good days and bad days. Yesterday for some reason was bad. Today I don’t have the aches, only nausea. I’m going to look in to more anti nausea remedies. Zoloft is only somewhat effective and I feel like it gives me the jitters. If I could string together some days where both pain and nausea were under control, it would help.

exbrnxgrl

This sounds a bit simple but ginger ale, in small sips, ginger tea and ginger chews have helped me with nausea. If it’s bad, Zofran works well (but it does give me a headache).

Cure-ious

It is undoubtedly worth asking your MO whether you might have acquired an ESR1 mutation. These are mutations of the estrogen receptor (ER) that are not found in the primary cancer, but are acquired as a result of using the AIs, because the mutant ERs are able to turn on genes even when estrogen is not around. Its a really common mutation and develops in up to a third of MBC patients. The SERM (tamoxifen-like molecule) lasofoxifene works really well on ESR1 mutant cancers, and faslodex will also work though maybe not as well. Two articles appeared today on OncLive talking about lasofoxifene and ESR1 mutants. There is a liquid biopsy that can be used to detect the mutation, if you remain bone-only and cannot do a new biopsy. Lasofoxifene is being tested in phase II ELAINE trial: NCT03781063.

https://www.onclive.com/web-exclusives/expanding-t...

https://www.onclive.com/web-exclusives/er-modulati...

Lasofoxifene was approved by FDA last spring for fast-track, its been around a long time and tested for other things, so it is well-known safe with few SEs, if they find it works well on ESR1 they will try to move it in quickly. As with everything else, it works even better in combination with CDK4,6 inhibitors.

https://www.targetedonc.com/news/fda-grants-fast-t...

DivineMrsM

Cure-ious, thank you for the insight and links. I will check them out, Your knowledge on so many aspects of mbc is amazing,

candy-678

Divine- Sorry you are having progression after so long stable. You have been given some good advise so far. I guess I would ask for Foundation One/liquid biopsy studies to look for mutations you could act on. My onc mentioned a PARP would be next for me, since that was recommended as a possible treatment on my F1 studies (done at diagnosis 2 years ago).

Yes, I did/do have increased pain in my spine a couple of inches above the bra closure. I did not have documented mets at that level, lower but not at that level. The Oct CT showed slight increase in liver met so we ordered a PET. The PET showed no uptake. In the liver or in the spine. So the pain??? I do have rheumatoid arthritis, so that ???? Who knows. Do we trust the scans?? Could the area be something but too small to be seen by scans yet??

Will be interested to hear what your onc suggests.

Bestbird

Divine, you've received excellent input. Here's a summary of therapies by line for postmenopausal MBC patients with HR+, HER2- disease. The list was reviewed and approved by Dr. Kevin Kalinsky, Medical Oncologist at Columbia Presbyterian Hospital in NYC. This information, along with cutting edge research, is in my book, "The Insider's Guide to Metastatic Breast Cancer," which is also available in a complimentary .pdf. For morde information, you and others are welcome to visit https://www.insidersguidembc.com/about (Also, if you haven't done so recently, please consider a biopsy to see whether the cancer's pathology has changed).

First Line Hormonal and Targeted Treatment Options:

A CDK4/6 inhibitor such as Kisqali (Ribociclib), Ibrance (Palbociclib), or Verzenio (Abemaciclib) in combination with an Aromatase Inhibitor such as Letrozole (Femara), Arimidex (Anastrozole), or Aromasin (Exemestane).

An Aromatase Inhibitor alone is also an option.

Faslodex (Fulvestrant) with a CDK4/6 inhibitor or alone.

Faslodex with Arimidex A recent study (SWOG 0226) reported that postmenopausal patients taking Faslodex and Arimidex as initial endocrine therapy had a median Overall Survival (OS) of 49.8 months compared with 42 months in the Arimidex-only arm, which is the longest ever reported for this type of patient.Therefore, this combination may be worth discussing with your doctor.

Tamoxifen (Nolvadex) or Fareston (Toremifene) alone (rarely used as a first-line therapy).

Second Line Hormonal and Targeted Treatment Options depend upon what endocrine therapy you have previously taken:

Possibly any of the above therapies.

Afinitor (Everolimus) with either an Aromatase Inhibitor, Faslodex, or Tamoxifen.

Verzenio alone (after disease progression on endocrine therapy and prior chemotherapy for MBC).

Piqray (Alpelisib) in combination with Faslodex if your cancer has a PI3K mutation (more about this below).

Third and Fourth Line Hormonal and Targeted Treatment Options depend upon what endocrine therapy you have previously taken:

Possibly any of the above therapies (although not all options are widely used in a third or later line setting).

Either Ethinyl Estradiol, Megace (Megestrol Acetate), or Halotestin (Fluoxymesterone).

Chemotherapy is usually prescribed after endocrine therapies have stopped working, or a clinical trial may also be a consideration.Once your cancer has regressed or stabilized, it may be possible to go back on endocrine therapy if sufficient time has elapsed and if your initial response to endocrine therapy had been favorable.

did you know?

If you have bone metastases, you should receive a bone-directed therapy such as Xgeva (Denosumab) or Zometa (Zoledronic acid) in addition to your other therapy.

If your cancer has progressed on first-line hormonal therapy and has a PI3K mutation, then you are eligible to take Piqray (Alpelisib) tablets along with Faslodex.Piqray is a PI3K inhibitor that has shown a clinically meaningful benefit in treating patients with this type of breast cancer.A diagnostic test called "Therascreen PI3KCA RGQ PCR Kit," has been FDA-approved to detect the mutation in a tissue and/or a liquid biopsy.

If you have a germline BRCA mutation, you may want to speak with your doctor about taking a PARP inhibitor such as Talazoparib (Talzenna) or Olaparib (Lynparza), which are FDA-approved for HER2 negative MBC patients with BRCA mutations.

Although very rare, if your cancer has microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) characteristics, and if you've progressed on prior therapy and have no satisfactory treatment options, the PD-1 inhibitor Keytruda (Pembrolizumab) is an FDA-approved option.

If your cancer has a Neurotrophic Receptor Tyrosine Kinase (NTRK) gene fusion without a known acquired resistance mutation, and if you've progressed on prior therapy and have no satisfactory treatment options, Larotrectinib (Vitrakvi) and Rozlytrek (Entrectinib) – oral tyrosine kinase inhibitors that act as an "on" or "off" switch in many cellular functions – are FDA-approved options.NTRK fusions are extremely rare, occurring in only about 0.5–1% of common cancers.

Sadiesservant

Divine,

I’m sorry to hear that you have increased pain. If it’s troubling you then an earlier scan is a good idea. That will help you to know where things stand. I understand that Verzenio takes about 4 months to show improvement so it may be working. It’s so hard for us to know for sure with primarily bone mets. I had early progression which likely made me overly vigilant. As a result, there have been numerous times over the last two years when I have had increased pain and/or symptoms but scans indicated I was stable. It’s hard to feel comfortable in the face of weird symptoms though.

Have you had any of the bone mets radiated? It may be possible that one or two lesions are messing with nerves if the pain meds aren’t working. Perhaps a consult with an RO would be helpful. The others have given you good advice in terms of options. Faslodex may be a good choice - I have been on it for almost two years and it held things steady after failing on the AI.

Finally, I hear you on the QOL issues with Verzenio. Quite frankly, I’ve found it to be a miserable treatment. I’m in a better place now at 200 mg in the evening but am still struggling with loss of taste, cramping, residual nausea in the mornings and mouth issues. Now it looks like my blood may not be tolerating it. It’s funny how different we all are. Some sail through treatments that others find intolerable and for some nausea is not a big deal while for others... Just know you are not alone. I have found this to be the most challenging treatment I’ve had to date and I include heavy duty chemo as stage II in that assessment.

Sending a virtual hug. Hope you are able to get to a better place in your treatment soon.

Pat.

Nkb

Devine- I hope that the Verzenio is still working, but, if not I would consider Afinitor/Aromasin. if you can do the PIK3mutation test and have the mutation ,then piqray, if you can't/don't do the test then the Afinitor. (from what I can tell the side affect profile of the Piqray looks worse- course its always if YOU get the side or not. ) a new study came out saying that the PFS for Afinitor after a CDK4/6 inhibitor was 11-12 months. there are many of us doing well on it. The reality is these drugs only work in about 40-50% of people to begin with, and then they eventually fail. my MO says I will be trying them all eventually. There is some thought that there is cross reactivity between the CDK inhibitors. I think that when an oral SERD is approved we may see some better responses to some of these meds.

I was hoping that a triplet would be the ticket, but, I heard a discouraging talk about that possibility, so hoping we can recycle some of these drugs. Hang in there. I hope you are having a good day today.

pajim

Ugh to being allergic to NSAIDs. That's a pain (which you know). There have to be other things besides Tylenol. Tramadol helps some people (me for one). Might I suggest a consult with a pain center or a palliative care service? And take Zofran. Please don't spend your days feeling sick. . .

QT314

Hi Bestbird. Great summary. I am interested to know why Capecitabine (Xeloda)isn't included in the list as my experience is that it is sometimes used as a 2nd line treatment if there has been significant progression on first line treatments.

DivineMrsM

Bestbird, as always, you are a wealth of information, Thank you, everyone, for your input, I'm going to write down the different options that have been laid out here so I can go over them with my onc next time I see her. I'm also mulling over the palliative route and will give it more thought after the first of the year.

Pajim, I'll ask for a tramadol prescription. It would be good to have on hand when needed. This week I've been having better days. Very little pain. Mostly fatigue and nausea. Zofran helps, but only so much. It may be a bit of overdosing. The onc gave me 8 mg pills and I see you can take 4 mg. I can be sensitive to some meds. I also have a prescription for 10 mg of compazine and cut one in half and was not debilitated the way I'd been when I took one full strength. Maybe I'll quarter them and take 1/4 in the morning and 1/4 in the afternoon. I'm going to do a bit experimenting with these anti nausea meds to try and get the most benefit. Tamping the nausea down, if and when I can, gives me a better outlook on life.

I had a dream last night about a rose bush shrub that was full of pink buds opening. I took that as a good sign my sights are looking up.

Kimchee

So has anyone gone back to old treatments with positive results ?