Bazedoxifene---why only one trial?

My two cents.

Why only one trial? - Pfizer is pervasively corrupt. Easier to hide/manipulate the results of only one trial.

Why with another drug? - Pfizer owns both drugs. Why only gouge for one drug, when you can gouge for two.

Why so many constipation trials? - It's the one market Pfizer can't corner and it's probably the topic of many board room discussions as to how to dominate that condition....do whatever it takes.

How will the Moonshot Initiative affect it? - It won't.

Would Pfizer co-operate? - Absolutely not.

The whole immunotherapy thing scares me for several reasons and like you mentioned, if that's what direction all of this is going to take, I'm disappointed...well, disappointed may not be the right word, but I am concerned.

I totally forgot about BZA. I still wonder how this drug ties into Dr. Craig Jordan's (Father of Tamoxifen) research on "estrogen induced cell death", if at all.

Are there any postmenopausal breast cancer patients taking BZA for osteoporosis?
Since the European Union approved BZA in 2009, it would be interesting to know if anecdotal evidence exists - supporting progression free survival (PFS) data - among the population of breast cancer patients taking it for osteoporosis.

I think Fallleaves did a good job to encapsulate some of the thoughts discussed in older BZA threads and raised some interesting questions.

At the 2015 SABCS last month, a Dana Farber group discussed BZA. Here's the Abstract.
P3-05-09 "Exploring bazedoxifene and palbociclib as potential therapeutic strategies for overcoming ESR1-mediated endocrine resistance"
Nguyen M, Buchwalter G, Luo F, Garraway L, Brown M, Jeselsohn R.
Dana Farber Cancer Institute, Boston, MA.
INTRODUCTION: Despite effective endocrine treatments, endocrine resistance remains a major clinical challenge. We and other groups have recently detected ligand-binding domain ESR1 mutations in metastatic estrogen receptor positive (ER+) breast cancers. Our preclinical studies showed that these mutations confer constitutive activity and relative resistance to tamoxifen and fulvestrant. In this study we sought to investigate therapeutic strategies to overcome resistance rendered by the ESR1 mutations. Since our previous studies showed relative resistance to tamoxifen or fulvestrant, we hypothesized that bazedoxifene, a high affinity third generation SERM/SERD could overcome resistance driven by the ER mutant resistance. Additionally, we hypothesized that inhibiting cyclin D1, a key ER transcriptional target gene and cell cycle regulator, is a second potential therapeutic strategy to circumvent resistance rendered by mutant ER. Therefore in this study we tested the effects of bazedoxifene, palbciclib and their combination on cell proliferation in the presence and absence of the ESR1 mutations.

METHODS: For this study we established doxycycline inducible MCF7 cell lines expressing the ER-LBD mutations (Y537S, Y537N and D538G) and WT-ER as control. Cell proliferation response to bazedoxifene, tamoxifen, fulvestrant, palbociclib and the bazedoxifene-palbociclib combination was evaluated.

RESULTS: Cells harboring mutant ER were relatively resistant to tamoxifen and fulvestrant, as expected, and remained sensitive to single agent bazedoxifene and palbociclib. The combination of bazedoxifene and palbociclib was found to be superior to the single agents and exhibits synergistic activity.

CONCLUSION: The combination of bazedoxifene and palbociclib inhibits mutant ER cell growth and other cell models of endocrine resistance and is a potential therapeutic combination.
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Ironically, the same time this BZA presentation was being made, Dr. Jordan (Father of Tamoxifen) and his research team were down the hall, presenting data on the paradoxical effect of Estrogen in breast cancer, found here, (i.e. Breast cancer cells once fueled by estrogen can be killed by the same hormone, raising the possibility that "estrogen therapy" after "estrogen deprivation" may overcome the cells' eventual resistance to hormone therapy.)
In that Abstract, they summarized by saying: "We conclude that, for the first time, we have observed the binding of a ligand to a receptor that changes conformation against time and evolves from an antagonist to an agonist conformation to trigger apoptosis. These observations have current relevance to the decryption of the protective effects of estrogen alone therapy against breast cancer incidence in the Women's Health Initiative (WHI) trial".
That large postmenopausal trial (WHI) launched in the early 1990's and is discussed at length here.

Duavee is BZA with estrogen. I don't think any studies have been done with Duavee and bc but it would be interesting to see a trial of the drug used after estrogen deprivation, particularly after an AI.

Intermittent estrogenic stimulation is the premise of the SOLE trial. The deprivaton part is done with letrozole.

Izzy,

This thread has been inactive for 4 1/2 years. If you don’t get a response you may want to consider starting a new one on the subject. Take care