Good News re: CDK4/6 Inhibitors & Overall Survival

[Bestbird]

Greetings,

If you have Hormone Receptor positive, HER2 negative MBC, some great news was shared at the ESMO conference this past weekend regarding Overall Survival with CDK4/ inhibitors. The information below has been incorporated into my book, “The Insider’s Guide to Metastatic Breast Cancer,” which is also available in a complimentary .pdf. For information about approved therapies and cutting edge research, please visit: insidersguidembc.com/about

Verzenio (Abemaciclib) and Faslodex: The Phase 3 MONARCH 2 randomized trial studied 669 HR+/HER2- pre-, peri-, and postmenopausal MBC patients who progressed on prior endocrine therapy and were then treated with Verzenio and Faslodex (Fulvestrant) vs. Faslodex + placebo. Median Progression-Free Survival (PFS) was 16.4 months for patients taking Verzenio plus Faslodex vs. 9.3 months for patients on Faslodex + placebo. The Objective Response Rate (ORR) was 35.2% for the Verzenio combination vs 16.1% for patients on Faslodex. After a 5-year follow up, patients taking both Faslodex and Verzenio had a median Overall Survival of 46.7 months. as opposed to 37.3 months for patients in the Faslodex+ placebo arm. Furthermore, patients on the combination were able to delay starting chemotherapy for an average of 7.3 months longer than those in the control group. From: cancertherapyadvisor.com/as... treatment/article/666229/ and med.stanford.edu/news/all-n...

Kisqali (Ribociclib) and Faslodex – postmenopausal women: In the MONALEESA-3 trial of 726 MBC patients, Kisqali in combination with Fulvestrant (Faslodex) showed an improvement in both Progression Free Survival (PFS) and Overall Survival (OS) in postmenopausal women with hormone receptor (HR)-positive, HER2-negative advanced breast cancer. The benefit was seen both in patients who had no prior treatment and in patients who had received 1 prior line of endocrine therapy. Overall PFS was 20.5 months for patients on the combination vs. 12.8 months for patients on the Faslodex only arm. Specifically among patients on first-line treatment, median PFS was significantly longer with Kisqali and Faslodex at 33.6 months vs. 19.2 months for patients on Faslodex alone. Importantly, there was an OS benefit with Kisqali and Faslodex across all patient subgroups. The OS has not yet been reached for patients taking the combination as first-line therapy, and the OS for patients taking Faslodex alone in the first-line setting was 45.1 months. Patients taking the combination in the second-line setting had a median OS of 40.2 months, vs. 32.5 months for patients taking Faslodex alone. From: healio.com/hematology-oncol...

Kisqali and Tamoxifen or an Aromatase Inhibitor – peri and premenopausal women: I’d previously reported that in the MONALEESA-7 trial, 672 pre- and peri-menopausal patients who had not received prior hormonal therapy were randomized to receive Kisqali or a placebo in combination with Tamoxifen (or Letrozole or Aromasin) and Zoladex, an ovarian suppression drug. The Kisqali combination resulted in 70.2% Overall Survival (OS) at 42 months vs. 46% OS in patients receiving hormone therapy without Kisqali. This corresponds to a 29% lower risk of death in patients receiving the Kisqali combination therapy. From: eurekalert.org/pub_releases...

[LouisaMay]

Hi Bestbird, Thanks for your great information as always. No mention of Ibrance (palbociclib)?

[Bestbird in reply to LouisaMay]

LouisaMay, News about Ibrance and OS came out last year, as reported in my Guide (excerpt below). As of now, all three CDK4/6 inhibitors have encouraging news regarding PFS and OS!

PALOMAIII study revealed that the combination of Ibrance and Faslodex resulted in a clinically meaningful improvement in Overall Survival (not just Progression Free Survival) among women with hormone receptor-positive, HER2-negative breast cancer whose disease relapsed or progressed on hormonal therapy. The Ibrance/Faslodex regimen extended median Overall Survival (OS) by an absolute difference of 6.9 months (34.9 months on the combination arm vs. 28 months on the Faslodex-only arm). Researchers observed even greater OS benefits among women with endocrine-sensitive disease (median, 39.7 months on the combination arm vs. 29.7 months on the Faslodex-only arm) and those with non-visceral disease (median, 46.9 months on the combination arm vs. 35.4 months on the Faslodex-only arm). From: healio.com/hematology-oncol...

[LouisaMay in reply to Bestbird]

Thank you xxx

[SoCalLady]

Thank you Bestbird for keeping us informed. We appreciate all your work and knowledge.

[Bestbird in reply to SoCalLady]

My pleasure! Good news is always a joy to share!

[MyMiracle13]

Thank you so much for sharing the good news! Can one change to Ribociclib after Ibrance/Faslodex fails?

[Bestbird in reply to MyMiracle13]

Ribociclib (Kisqali) is a twin drug to Ibrance, so there wouldn't be a good reason to try it once Ibrance fails. Verzenio works somewhat differently to Ibrance and Kisqali, although it too is a CDK4/6 inhibitor, and hence it can be tried after Ibrance or Kisqali fails. There's more about this in the Research section of my book.

[MyMiracle13 in reply to Bestbird]

Thanks for the reply😄

[Prasath_sas]

My mom is taking only Femara for the past 3 years and she is doing good an NED as per last PET Scan took on 2018. Any idea on how much time will Femar alone will be effiective

[kduck in reply to Prasath_sas]

Wow! Thank for posting, im only taking femara and I felt like I should be taking more. I've been taking it for about 2 months. I was just taking falsodex, but I had lymph nodes to show up positive for breast cancer.

[PJBinMI in reply to Prasath_sas]

I was diagnosed with mbc before meds like Ibrance, Afinitor, Kisquali, etc existed and I got almost five years from Femara along with bone meds. I have lobular mbc, E + originally P + now P- her2neu -, extensive bone mets. Faslodex worked for me for over 9 years, with Ibrance for a few cycles in 2016 but damaged my lungs. Now on Exemestane for almost 2 years. Still only bone mets and never any symptoms from the mets.

[myrtice in reply to PJBinMI]

Thank you for sharing such encouraging news. Day 9 in my journey and all is well. Have blood test Monday. Hope you have a wonderful Tuesday.

[kearnan in reply to PJBinMI]

Hi. Curious to know about your remark that Falsodex damaged your lungs. I have mets in my lungs. I was first put on Ibrance (with falsodex) but had to stop after three cycles, not to progression but due to extremely low wbc and how sick I got on my week off and it caused an infection to flare up. I hated Ibrance. I am now on Verzenio and still on Falsodex injections. I could not handle the highest dosages 150 and 100 mg (both twice per day). so my onco put me on 50 mg. twice per day with no weeks off and I am doing better on this than Ibrance physically. I have been on it for about six weeks now. But recently had a CT scan done and my onco said that there appears to be major inflammation. (Pasted and copied from an email from my onco).

"There was some evidence of possible recent respiratory infection/inflammation in the lungs, but they did not think this was related to the breast cancer. "

All in all, although the meds switched and I was off the meds after developing a different infection on Ibrance which took 4 months to clear up, I was still ONLY then getting my falsodex injections. All in all I have been on falsodex for about a year and a half? May I ask what type of damage was done to your lungs and how you know it was from the falsodex? So many women are on it and this is the first I have seen that mentioned. Considering what she wrote above, I am just wondering. Thank you.

[Bestbird in reply to kearnan]

Recently the FDA issued a warning about CDK4/6 inhibitors:" Ibrance (palbociclib), Kisqali (ribociclib), and Verzenio (abemaciclib) used to treat some patients with advanced breast cancers may cause rare but severe inflammation of the lungs. " From: fda.gov/drugs/drug-safety-a...

That said, they feel that the potential benefits outweigh the risk.

[kearnan in reply to Bestbird]

True. There are always going to be some side effects, some worse than others but for the very few. Thanks.

[SoCalLady in reply to kearnan]

Hi kearnan, I didn't get the impression from PJBinMI that the Faslodex gave her lung damage, because of her comma in the sentence, that it was Ibrance causing the damage. But I'm probably wrong. Maybe PJBinMI could clarify. Also, I would like to know why onc decided on Exemestane.

[PJBinMI in reply to SoCalLady]

Yes, it was the Ibrance that my onc an other docs believe caused the Interstitial Lung Disease. And I've been off Ibrance for 3 years without improvement in the lungs. I found Faslodex easy to be on.

[Prasath_sas in reply to PJBinMI]

Hi PJBinmi, many thanks for the reply, your words give me more hope

[SoCalLady in reply to PJBinMI]

In all these years, have you not had any bone pain?

[PJBinMI in reply to SoCalLady]

I've not had pain in any of the places with bone mets. I did have some joint pain while on Letrozole, but Celebrex helped that. I've just been really lucky and not had symptoms from the cancer itself. Side effects from meds, yes, but nothing from the cancer itself. Isn't that crazy!

[mariootsi in reply to Prasath_sas]

Femara alone after initial dx lasted 5 years as NED. But last April had mamo and found cancer in my other breast and further testing showed spread.

[Bestbird in reply to Prasath_sas]

Great news about your mother's response to Letrozole (Femara!) Some patients can remain on it for many years, and there's no way of predicting how long the response will last. Wishing her a durable response!

[mariootsi]

I can't consider survival in months! It's too depressing. I'm thinking in terms of years! I have too!

[backgreen]

Ibrance failed my wife after only 3 months her Onc seems to think Verzino

and Kisqali would do the same..this seems to suggest otherwise?

[Hidden in reply to backgreen]

Hi Backgreen -

My onc told me - as Bestbird also comments on, above - that Verzenio is not a direct substitute for Ibrance and can be effective even after Ibrance fails. I would definitely take this up with the docs.

Question: When you say Ibrance "failed", am I correct that you mean that she had progression?

If this is the case, I think you should know that many docs (and women, here) say that this type of treatment can take several/many months (e.g. 6 months is a common duration) to really kick in.

I began Ibrance/Letrezol in April of...2015?...in October or November my scans showed widespread bone mets, whereas previously I had just one tumor. My doc suspected that these had been there all along, just too small to detect, so we did not change out the drugs. I began to improve after that, and kept improving for almost two years, followed by a gradual worsening. I think it's fair to say that the decision at that one juncture added years of high-quality time to my life.

The number one piece of advice I give people is not to switch any sooner than you have to. I've learned on this site that the reason why some docs are quick to switch is because they don't understand that the hormone-related treatments can take a long while to work. You're slowly starving the tumors, I think. I've read comments from wise women here who emphasize that it is key to have an oncologist who specializes in breast cancer because they are more familiar with this factor.

Best wishes to you both.... Lynn

[Bestbird]

There are many other options to try before considering Verzenio, which works slightly differently than Ibrance and Kisqali. Examples include Faslodex, and the Aromasin/Afinitor combination. For a comprehensive list of treatment options, please see my Guide.

She should also be tested gor grrmline mutations such as BRCA and PI3K because there are approved drugs targeting these mutations.

Good wishes.

[needabreakfromcancer]

Unfortunately none of the aromatase inhibitors worked for me. In fact, the Exemestane caused a lot of damage, that I fear is permanent. It presented vision and balance problems, which I mentioned to both of my oncologists. They were both unaware of this side-effect and one of them ordered it for me! I was on it for a year and should have been taken off of it immediately. I am so upset that doctors do not know the side-effects of these very powerful and often, dangerous drugs! I was diagnosed by a balance expert that told me that some medication I had taken had caused damage to my brain and that my cerebellum was sending mixed messages to my eyes. My eyes themselves are fine, but don't get the correct message from my brain. As a result, I feel normal when I sit, but the minute I stand, or sit, without support, my body sways and I feel like I am going to fall. It is hell! If I didn't have this, I would feel pretty normal. I do have fatigue, but find when I go out and live my life, it is gone.

[Bestbird in reply to needabreakfromcancer]

I am very sorry to hear of your significant sise effect, and hope that perhaps a good neurologist may be of help. Wishing you a recovery.

[needabreakfromcancer]

Thank you. I hope to see one in Denver. He told my oncologist that he wonders if a medication for migraines (tho I don't have them) would block the bad messages. I just hope it won't make it worse. I have a fear of drugs hurting me, not helping me, for good reason.

[Bestbird in reply to needabreakfromcancer]

Wishing you the best going forward!

[Red71]

I’m the same as you as far as the pain goes. I was in extreme pain when diagnosed, am much better now after radiation to my back lesions, but I will never be pain free. Not to be in pain would make this so much easier!

[Hidden]

Bestbird...THANK YOU! While I've certainly been grateful for the PFS gains from Ibrance, I did have a niggly concern re: OS, since last I checked that was an unanswered question. But you gave us the answer! Thanks!