palbociclib (Ibrance), letrozole and Pembrolizumab (keytruda)

Hi Stephanie,

Sure, are you kidding?! Now that I see it, hell ya, I'm interested in this trial too! However, the write-up indicates that it is for metastatic patients with stable mets who are NOT responding to Ibrance- Femara, did I read that correctly? Seriously, I think we all should get immunotherapy ASAP, before tumor burden gets too high and there have been too many previous treatments, the immune system can be working on the cancer for years. If you do get in the trial, I would add the probiotic Align (bffidobacterium) because that strain of bacteria was shown to synergize with immunotherapy drugs, in fact immune cells need this particular bacteria in the gut to be activated- here is a link about that:

https://www.ncbi.nlm.nih.gov/pubmed/26541606

I am excited to consider a trial, and will ask my MO about this Monday, any other info about it? your oncologist sounds very good?..

Stefanie,

This sounds like a great opportunity. I am monitoring some NIH immunotherapy studies and would ultimately like to do one. The one I have the most interest in requires that I first fail a chemo. I am on Xeloda but it is still working for now. One factor to consider is that I have heard that immunotherapy is more effective when the immune system is strong (before it is beaten down by more mets and extensive treatments). Another factor is that I have heard that's many of the immuno studies will rule out people who have previously been treated with immunotherapy, meaning one should choose wisely which immunity study to try. I haven't looked into this to confirm if it is true though. I read it in article about advances in immunotherapy over the last few years. Good luck determining whether to proceed. The good news is you are stable with a minimal tumor load! I hope that lasts for a very, very long time, regardless of whether you do the trial.

Cure-ious you make a good point when you note that once you do one immunotherapy trial, you probably are not eligible for another one. It's important to pick your trial. This one looks to me like someone said - hey Keytruda is FDA recently approved and Ibrance is recently FDA approved, I wonder i they work together? It was easy to get approval for the trial, since the two drugs are already FDA approved. The drug companies were likely happy to go along. But I don't see disruptive science behind the combination.

I too wonder if Keytruda and Ibrance work synergistically, but I would not use my one opportunity at immunotherapy on that logic.

There are interesting questions of strategy when it comes to getting yourself into trials generally and immunotherapy trials specifically. Vaccines seem to work better when you have little or no disease. They work slowly and don't seem to be able to penetrate tumors, but they can control micro metastasis. Other kinds of immunotherapy strategies seem to work better on advance cancers that have been mangled into something that the body recognizes as Other. But even so, established tumors are hard for the immune system to infiltrate. What stage is the best stage for getting into an immunotherapy trial is something I trying to figure out.

One issue for me with immunotherapy is that the brightest minds don't see ERPR+ as low hanging fruit at the moment. There are currently very few trials for immunotherapy on ERPR+ breast cancer. As long as the standard therapies are working, that is another reason to wait and see.

That said, I do spend a lot of time reading up on what my options are next. If letrozol and ibrance fail, they will put me on faslodex. Possibly with Ibrance. Unless I push a different plan. The question is do I push to get on a next generation therapy early through a trial, or do I take the current line of treatments as far as they will go before I put myself in a trial. Not sure.

There are very few trials for anything that will accept me until my first line of treatment (Ibrance/letrozol) has failed so that happily delays the question, perhaps indefinitely.

Interested in everyone's thoughts.

>Z<

You raise good points as always Cure-ious. I looked through three clinical trials watch list and noted some relevant inclusion and exclusion criteria. I've seen trials with strict exclusions regarding prior immunotherapy, but those exclusions are not there in the trials on my short list.

Keytruda/Ibrance/Letrozol

Inclusion: Stage IV metastatic ER+HER2- breast cancer

Inclusion: Presence of measurable disease meeting the following criteria: at least 1 lesion of > 10 mm

Inclusion: Patients must have been undergoing treatment with letrozole and palbociclib for >= 6 months with SD per RECIST version 1.1 and have tumors that have ceased to decrease (up to 20% of tumor growth allowed)

Inclusion: Received 1-3 lines of previous therapy including endocrine and/or chemotherapy in advanced setting

Exclusion: Previously received pembrolizumab or other anti-programmed cell death-1 (PD-1) or anti-PD-L1 immunotherapy

Tumor Infiltrating Lymphocytes

Inclusion: Breast and Ovarian cancer patients must be refractory to both 1st line and 2nd line treatments and must have received at least one second line chemotherapy regimen.

Inclusion: At least one lesion that is resectable for TIL generation

Exclusion: no exclusions related to prior immunotherapy

Vaccine Therapy (STEMVAC) Trial

Inclusion: Patients with stage III-IV HER2 negative breast cancer treated with primary or salvage therapy and now have: No evidence of disease (NED), or Stable bone only disease

Exclusion: no exclusions related to prior immunotherapy

Cure-ious - The IMPassion trial that you refer to is for TNBC, like most of the immunotherapy breast cancer trials right now. It seems that TNBC finally caught a well deserved break. For ERPR+ HER2- there are mostly new flavors and combinations of chemo. But there are a few transformative trials. Let's do keep an eye out for them. In the meantime we have the trifecta of CDK 4/6 inhibitors (ribociclib, palbociclib and abemaciclib) and a lot of tried and true A/I. I expect many of us will hold out for a long time with the drugs we have and a lot of broccoli.

That said, with PR- cancer I think the TNBC research will likely benefit you. Keep an eye on it.

>Z<

How interesting Cure-ious. Please keeps us informed on your decisions and experience.

>Z<

My mom has ER+PR+HER- stage IV Mets to bone, brain and questionable spots on adrenal. She's had a pretty rough time very little moments of good news. Was told there is many may options for treatment. She was on let letrozole then ibrance and now these shots (can't recall the name) 2 shots in the bottom. All which has failed the NP said Xeloda or comfort care which has me baffled and upset because this doesn't sound like loads of options to me and her brain Mets is stable and all other areas are fairly stable or very small. I asked about the keytruda option and was told that isn't an option for er+pr+her2- breast cancer patients. I asked about other immune building options along with treatment and she acted like there wasn't any. I see your cancer is same as my mom's any advice?