Ribociclib (Kisqali) is Now FDA-approved with letrozole

Bestbird

In March 2017, the CDK4/CDK6 inhibitor formerly known as Ribociclib (now called KISQALI) has been FDA-approved in conjunction with Letrozole as a first-line therapy for postmenopausal mbc patients who are hormone receptor positive and HER2 negative.

IBRANCE, another CDK4/CDK6 inhibitor, was approved in 2015 in conjunction with Letrozole as a first line therapy, and then in 2016 as a second-line therapy in conjunction with Faslodex.

Abemaciclib is a CDK4/CDK6 that may be used alone, but it has not yet been FDA-approved.

When deciding upon first line treatment with letrozole and either IBRANCE or KISQALI, the clinical trial information below which depicts respective outcomes and side effects may be taken into account along with cost and availability considerations.

MONALEESA-2 (Phase III Trial), which compared KISQALI (Ribociclib) plus Letrozole, vs. Letrozole alone

This was a randomized, placebo-controlled, phase III trial of 668 postmenopausal hormone receptor positive, HER2 negative mbc patients that had not received prior systemic therapy.Median Progression Free Survival (PFS) was 25.3 months with the KISQALI (Ribociclib) + letrozole combination vs 16 months for the letrozole-only group.The most common significant adverse events were neutropenia (59%), leukopenia (21%), hypertension (10%), and elevation of a liver enzyme called alanine aminotransferase (ALT) (9%).Permanent discontinuation rates due to adverse events were 7.5% among patients taking both KISQALI and letrozole vs. 2.1% among patients in the Letrozole-only group.

The new drug is accompanied by warnings and precautions about QT interval prolongation (which can lead to a type of cardiac arrhythmia that is a risk factor for death) and "hepatobiliary" toxicity (having to do with the liver plus the gallbladder, bile ducts, or bile).From:http://www.medscape.com/viewarticle/877177

PALOMA-2 (Phase III Trial), which compared IBRANCE (Palbociclib) plus Letrozole, vs. Letrozole alone

This was a randomized, placebo-controlled, phase III trial of 666 postmenopausal hormone receptor positive, HER2 negative mbc patients that had not received prior systemic therapy. Median Progression Free Survival (PFS) was 24.8 months for the IBRANCE (Palbociclib) + Letrozole group vs 14.5 months for the letrozole-only group.Common adverse events among patients taking IBRANCE +letrozole were neutropenia – (low levels of neutrophils which are a type of white blood cell) (79.5%), fatigue (37.4% ), nausea (35.1%), joint pain (33.3%), and hair thinning/loss (32.9%).Permanent discontinuation due to adverse effects was 9.7% in patients taking both IBRANCE and Letrozole, vs. 5.9% among patients taking letrozole alone.(It has since been determined that patients taking IBRANCE may also be at increased risk for blood clots).From:http://meetinglibrary.asco.org/content/165131-176andhttps://www.ibrance.com/side-effects

Best to all!

RosesToeses

That's exciting, thanks for the update (and really, thanks for all the excellent info you post here!).  I failed Ibrance because I couldn't keep enough white blood cells to continue so I've been sort of secretly rooting for some of these other CDK4/6 drugs in hopes that they might be a possible future option for me, but either way it's terrific for the MBC community as a whole to have some more choices out there!

RosesToeses

Also, any idea at all how to pronounce "Kisqali"?  I have to admit I see a few options but nothing I'd be willing to run with!

JFL

Thanks for informing us, Bestbird! I, too, have cycled through Ibrance and am hoping there are alternative CDK4/6 inhibitors in the pipeline that work on people who have become resistant to Ibrance. Any indications yet whether the medical community believes that there may not be full cross-resistance with ribociclib and Ibrance or the others in trials, so that people may cycle through CDK4/6 inhibitors?

zarovka

I thought I a Kisqali once while walking deep in the woods of Manitoba on a snowy night, but it turned out to be a deer.

In all seriousness, I think what we have here is a choice between neutropenia and vomiting, but otherwise the drugs look very similar. IOW I don think Ribociclib will work if Ibrance did not .... unless you had to drop Ibrance due to neutropenia.

>Z<

Moderators

Hi all! We thought you'd be interested in Breastcancer.org's article on this news:

Kisqali Approved by FDA to Treat Hormone-Receptor-Positive Advanced-Stage Disease
March 15, 2017
Kisqali was approved by the FDA on March 13, 2017 to be used in combination with an aromatase inhibitor to treat advanced-stage or metastatic hormone-receptor-positive, HER2-negative breast cancer that hasn't been treated with hormonal therapy yet in postmenopausal women. Read more...