SABCS 2019 Recap

Bestbird · January 2020

Greetings and Happy New Year!

With the start of the new year, I wanted to provide a recap of the 2019 San Antonio Breast Cancer Symposium that was held in December. It is the largest breast cancer conference in the world and is attended by physicians, researchers, and patient advocates. The results of clinical trials are often disclosed at SABCS before they're available anywhere else, and there was a great deal of information provided about MBC.

Here's my summary of MBC news that was conveyed at the conference last month: https://www.insidersguidembc.com/sabcs-2019

I hope this information will be helpful for patients and their medical teams!

BevJen · January 2020

Bestbird,

Thank you so much for this information. I met with my MO last week and asked her about MBC insights from SABCS. She told me that there had been a lot of info about MBC patients, mentioned a couple of things quickly, and was really just not that informative. Now I am armed with your info which will certainly help me in asking about specific treatments. So -- thank you from all of us!!!

cowgal · January 2020

Thank you so much for summarizing this!

Cure-ious · January 2020

Outstanding Anne! Clearly organized and very comprehensible

Anonymous · January 2020

Thank you so much!

SandiBeach57 · January 2020

Thank you Anne.

This is extremely helpful information and I am printing it somehow..

My question is regarding the Moffitt trial..Verzenio after Ibrance failure. How does one know 100% if the culprit is Ibrance and not the antihormonal? Is the biomarker that reliable?

S

MJHJAN1014 · January 2020

Thank you very much, Bestbird!

Bestbird · January 2020

So glad the information is helpful!

SandiBeach5, although I'm not a scientist, I can say that although Verzenio is a CDK4/6 inhibitor, it works somewhat differently from Ibrance and Kisqali.

We know that an ESR1 mutation can be a sign of endocrine therapy resistance precipitated by taking Aromatase Inhibitors, and yet some patients with this mutation had a durable response to Verzenio. We also know that patients with an ESR1 mutation can respond to Faslodex. So it's not totally surprising that some patients with this mutation had a notable response to Verzenio..

The following are indicative of CDK4/6 resistance, although I'd be reluctant to put a stake in the ground saying that Verzenio might not work for these patients, as it seems to have properties for efficacy that are not yet clearly elucidated.

Researchers have identified the following biomarkers that may be indicative of resistance to CDK4/6 inhibitors:

De Novo (Initial) Resistance:

Rb1 loss

FAT1 loss via the Hippo Pathway

CCNE1 overexpression

FGFR1 amplification

Acquired Resistance:

Rb1 loss

ERBB2 (HER2) mutation

PTEN loss of function mutations

AKT amplification

AURKA amplification

SandiBeach57 · January 2020

Thanks Anne for taking time to write that explanation.

I still get confused when progression is noted while on Ibrance/Letrozole (aromatase inhibitor). Is the assumption is that Ibrance failed along with the AI? Is it just an educated guess or do our MOs rebiopsy and look for those specific CDK 4/6 mutations along with the ESR1?

I would hate to switch from Ibrance to Versenio without a legitimate marker or proof that Ibrance no longer worked. So the Moffitt trial puzzles me.

I have your book by the way and use it frequently. What an amazing collection of very useful information!

S

JFL · January 2020

Thanks, Bestbird. This is very well-written and helpful. A lot of good information and updates this year. I hope some of these potential treatment options can move along the trial and approval process more quickly.

It is interesting about the listed mutations/amplifications that may signify resistance to certain therapies. Just as trials have proven that certain targeted therapies do not work for everyone with the particular target mutation/amplification, it seems some targeted therapies do work despite someone having one of the mutations/amplifications identified as those that may signify de novo or acquired resistance to a certain therapy. I had a good run on Ibrance despite having one of the amplifications on the de novo resistance list above. There may be trends/patterns but it seems there are no hard-fast rules with any of these amplifications/mutations. Everything is such a moving target and enigma when it comes to MBC, unfortunately!

Iwrite · January 2020

Thank you Anne! This is valuable information

Bestbird · January 2020

SandiBeach, it's indeed confounding when a combination of drugs stops working because no one really knows whether it's one drug, the other drug, or all drugs in the mix. And to JFL's point, just because someone has a biomarker that may indicate resistance to a type of drug, that doesn't necessarily mean that the patient will not respond to that drug.

Back to SandiBeach's question: for example, when a patient taking Ibrance and Arimidex stops responding, my guess is that the patient will no longer respond to AI's. The reason for that conclusion is that, unlike CDK4/6 inhibitors which need to be paired with endocrine therapy in order to work, an AI can work by itself. So if a combination of an AI and a CDK4/6 inhibitor stops working, it may make a degree of sense to pair that CDK4/6 drug with Faslodex, which can still work after resistance to an AI. And Faslodex can also be effective in and of itself. Just my perspective!

Chicagoan · January 2020

Bestbird-Thank you for all your work. This summary is very helpful.

SandiBeach57 · January 2020

Bestbird/Anne..you are an amazing woman. Thank you.

candy-678 · January 2020

Bestbird--- I have been wondering about the SABCS meetings and the take-aways for MBC. I have your book in print, but wondered too about updates. I downloaded the current updates linked above so now I am armed with the latest information. I know my MO did not attend the Conference. I do not know how much she stays informed of the latest advancements. Thank you Bestbird for all your hard work !!!!!!

S3K5 · January 2020

Bestbird, thanks for the SABCS summary and explanation on CDK inhibitors. I was on Ibrance and faslodex which failed after 15 months of stable bone mets. Then I was taking Verzenio which didn't do anything for my bone mets, which is not surprising but my ex-MO insisted that I try it. Within 3 months the cancer had spread from bones to liver. Now I am at MSK where they are open to patients being on clinical trial. Hopefully I may be a candidate for one the new ones you mentioned.

ShetlandPony · January 2020

Bestbird, you really are The Best!

On the subject of resistance, I had Foundation One genomic testing at original mbc diagnosis. Hardly any mutations of note. Did Taxol and achieved NEAD. Then after Ibrance + letrozole (2 years) and Afinitor + Faslodex (4 months) failed, my Foundation One re-test showed an ERBB2 mutation. Bingo. Xeloda worked for 2 years, and now my onc nurse is working on getting me Neratinib to address the ERBB2 mutation since that may be the driver. Not sure yet whether to combine it with a chemo, or with Faslodex.

Bestbird · January 2020

candy-678, I'm glad to hear that you find the book useful! What I suggest to people who have the book is to look at the complimentary .pdf whenever they want to check for new information, since it's not practical to keep purchasing the book (all three manuscripts - paperback, eBook and complimentary .pdf are kept to date).

So for example someone who has the book and has HR+, HER2- MBC and is facing a treatment change may want to look at chapters in the .pdf regarding standard therapies for this subtype, as well as research findings. The patient can either make notes in the paperback, or print relevant pages from the .pdf to tuck into the book if there's anything new. The .pdf is located at: https://www.insidersguidembc.com/order

SandiBeach57 · January 2020

Thank you. I have the book and now how the pdf site bookmarked so I can take notes in the margins.

There is constantly new info and I really appreciate that you are keeping the data current.

Frisky · January 2020

bestbird, thank you so much for all the great work you're doing. I'm very grateful to be able to read about the new medications and the results of the clinical trials. You are indeed the BEST!

Bliss58 · January 2020

Bestbird, thank you so much for this SABCS summary information. And as always, thank you for your wonderful updated MBC guide. You provide such valuable information for all of us. You are amazing and a treasure!