CDK4/6 Treatment After Prior CDK4/6 Failure

[Bestbird]

Many hormone receptor positive, HER2 negative MBC patients who have undergone endocrine therapy with a CDK4/6 inhibitor have wondered whether taking a CDK4/6 inhibitor after failure with a prior CDK/6 inhibitor might be of any benefit. In an effort to answer this question, two recent studies evaluated patients who took a CDK4/6 inhibitor after failure with a previous endocrine therapy/CDK4/6 combination. The encouraging results of these studies are provided below, and are also in my book “The Insider’s Guide to Metastatic Breast Cancer” which contains detailed information about approved therapies, cutting edge research, and more. For additional information about the book (and a complimentary .pdf), please visit: insidersguidembc.com/about

Kisqali (Ribociclib): The TRINITI-1 Phase 2 study evaluated 44 men and postmenopausal women with HR+, HER2− MBC whose disease progressed on up to 3 lines of prior hormonal therapy (including a CDK4/6 inhibitor) and up to 1 line of prior chemotherapy. The patients were given a combination of Kisqali, Afinitor, and Aromasin, and 17 patients (40.5%) had clinical benefit by local assessment. Furthermore, the median Progression Free Survival (PFS) was 8.8 months, which demonstrated promising clinical benefit and tolerability of this combination despite prior treatment with a CDK4/6 inhibitor. From: cancerres.aacrjournals.org/...

Verzenio (Abemaciclib): From Feb. 2015 to Jan. 2019, a study evaluated clinical outcomes in patients with HR+/HER2- MBC who received Verzenio after progressing on either Ibrance or Kisqali in combination with endocrine therapy. Although 20 (34%) of the patients on Verzenio had disease progression in less than 3 months, 21 patients (36%) had a treatment response duration exceeding 6 months - including 10 patients who remained on treatment at interim analysis (range 181-413 days). The median PFS on Verzenio following a prior CDK4/6 inhibitor was 5.8 months. From: meetinglibrary.asco.org/rec...

[SoCalLady]

Okay Bestbird, I'm trying to wrap my arms around this but they're getting tired. Can you summarize this in a non-clinical way. Thanks.

[Bestbird in reply to SoCalLady]

Sure! Because CDK4/6 inhibitors are similar in many ways (although Verzenio differs somewhat from Ibrance and Kisqali) researchers and patients have been wondering whether a patient can take a different CDK4/6 inhibitor after prior failure with a CDK4/6 inhibitor. In the above 2 studies, the results were encouraging. However, lots of additional studies need to be done.

[SoCalLady in reply to Bestbird]

Thank you for making it so simple. I do understand now. I wonder if being off one for awhile before you start the other would be helpful.

[Bestbird in reply to SoCalLady]

Great question! Hopefully more will be known with future studies.

[Pbsoup]

Hi Bestbird!

This is such great information. Thanks for all that you do!!!

I had slight progressio in December (still in bones, but a couple of new spots) after 18+ months on Ibrance/Anastrozole. My dr. has me on Faslodex alone now for a couple of months, markers are stable but not declining, and we are talking about starting a CDK4/6 again to see what happens--he has had success doing this apparently, but it makes me nervous as it doesn't seem to be standard of care. That said happy to ride this horse as long as possible...

I have seen similar research to what you shared in this post from a few years ago, but wondered if in your travels you have come across anything more up to date about benefits-- or not-- of restarting or switching to a new CDK4/6 post progression? It seems like Kisqali is promising??

I tried to do my own research, but only found trials in progress--so maybe there is nothing definitive yet?

Am not at all asking for medical advice!!! Just wondering if there are breadcrumbs of information I can send my doctor as we discuss next steps.

Thanks! P

[Bestbird in reply to Pbsoup]

Pbsoup, all research that I come across is in my Guide, which was used as a base for the above excerpts. Please also consider getting checked for tumor and inherited mutations if you haven't already done so, as there are approved therapies for the PIK3CA and BRCA1/2 mutations, for example. If you'd like more information about approved therapies, finding clinical trials, and cutting edge research, please check "The Insider's Guide to Metastatic Breast Cancer."

Good wishes!

[Pbsoup in reply to Bestbird]

You're a rock star. Thanks so much!