Cyclin-dependent kinase 4

The ATAC and BIG-98 study demonstrated that aromatase inhibitors and astrazole-letrazole were superior to tamoxifen with a hazard ratio of about 0.81%.

More recently, we've seen CDK4-6 inhibitors in combination with endocrine therapy approved for early breast cancer.

They've increased efficacy but also have associated toxicities.

In early breast cancer, the intent is curative, but up to a quarter of patients can have disease recurrence within five years.

So with this handed to Dr. Hurwitz, we can talk about how this fits in and how LIDERA population is different from Natalie and Monarchy.

Thank you, Aditya.

I think immediately I reflected on the fact that we also have the use of CDK4-6 inhibitors in the adjuvant setting.

And this study did not test in the main study, giridastrin combined with the CDK4-6 inhibitor.

So this trial is enrolling patients who have up to T3 size tumors, who have Multiple nodes, so N2 or N3 or T3 with other high-risk features.

And patients have a recurrence score 0 to 25 and are randomized to what we might think of for these high anatomic risk as standard of care, chemotherapy, endocrine, and CDK4-6 inhibitor versus omission of chemotherapy, endocrine therapy, and CDK4-6 inhibitor.

So we await results of this really important trial.

Now, as I alluded to, I think we're all familiar with hormone receptor-positive breast cancer having a very long tail risk of recurrence.

I'm in the not category.

I'd like to see some data that these actually impact outcomes before patients are having this done routinely.

This is adjuvant CDK4-6 inhibitors.

And these are our data sets.

Multiple nodes, so N2 or N3 or T3 with other high-risk features.

And patients have a recurrence score 0 to 25 and are randomized to what we might think of for these high anatomic risk as standard of care, chemotherapy, endocrine, and CDK4-6 inhibitor versus omission of chemotherapy, endocrine therapy, and CDK4-6 inhibitor.

So we await results of this really important trial.

Now, as I alluded to, I think we're all familiar with hormone receptor-positive breast cancer having a very long tail risk of recurrence.

I'm in the not category.

I'd like to see some data that these actually impact outcomes before patients are having this done routinely.

This is adjuvant CDK4-6 inhibitors.

And these are our data sets.

Multiple nodes, so N2 or N3 or T3 with other high-risk features.

And patients have a recurrence score 0 to 25 and are randomized to what we might think of for these high anatomic risk as standard of care, chemotherapy, endocrine, and CDK4-6 inhibitor versus omission of chemotherapy, endocrine therapy, and CDK4-6 inhibitor.

So we await results of this really important trial.

Now, as I alluded to, I think we're all familiar with hormone receptor-positive breast cancer having a very long tail risk of recurrence.

I'm in the not category.

I'd like to see some data that these actually impact outcomes before patients are having this done routinely.

This is adjuvant CDK4-6 inhibitors.

And these are our data sets.

Yeah, no, I think it is such a Beautiful conversation that we'll dovetail again into because we were talking about in the early stage setting, you know, the lead time, like you detect something and what can you do about it? We couldn't do anything about it yet in the early stage with the tumor-informed assay we were saying, right? But in the metastatic setting, we've at least moved a step forward in the right direction in that we have been able to do something about the lead time in some ways, right? And that's where the Serena 6 trial is very relevant because as we know, this was a phase three trial that just recently received FDA accelerated approval this past month, September.

And the trial really looked at over 3,000 patients who have been on their first line therapy with a aromatase inhibitor and a CDK4-6 inhibitor for at least six months.

And if they've been for six months, we then start doing the testing with ESR1 mutation serially every two to three months on study.

And if there is an emergence of ESR1 mutation, but no radiological progression.

For ribocyclic, we do three EKGs when the patients start to make sure that we do the EKG monitoring for the package insert.

Now, Serena 6 had 24 patients with ribocyclib.

So all CDK4-6 were allowed.

Majority were palbo.

Over the last five years, and I think I use this, and I say this quite often in my clinic rooms, is I think during COVID, a lot of cancer research has happened just because, you know, we couldn't see patients.

So let's think about research, right? So we've got so many, as you said, CDK4-6 inhibitors.

We've got anti-HER2 inhibitors.

therapies.