Everolimus

So they took 373 women.

having advanced breast cancer, they had failed the two standard therapies and they randomized them to receive standard endocrine therapy plus Everolimus or this new agent, Gritostant plus Everolimus.

With standard therapy, the progression-free survival was about 5.5 months.

With the addition of Geratostrat, it increased to 10 months.

In combination with Pembro for RCC, it is 20.

In combination with Everolimus, it is 18.

So this is, you know, kind of, you know, on the higher end of starting doses for linvatinib.

You know, I think 24 milligrams is the single agent dose of linvatinib for RCC.

This is an important study because we know in the first line setting, we have nevo-ipi, we've got axipembro, we've got lenvatinib and nivolumab, and we have those combinations, cabo and nivolumab.

So we have those combinations, and we don't know what to do when you progress on those combinations.

So we have a study of belzutafan after two lines of treatment, one of which was a PD-1, one of which was a VEGF-TK that shows it's better than Everolimus, which Everolimus is maybe not a great drug.

As they talk about in this study, Everolimus, it's an mTOR inhibitor.

The next generation of studies should investigate whether selective B-cell inhibition can deliver sustained disease control, less treatment-related injury, and safer long-term immune preservation.

Giridestrin plus Everolimus in Advanced Breast Cancer by Erica Mayer from the Dana-Farber Cancer Institute, Boston, and co-authors.

Worldwide, the standard approach to first-line treatment of patients with estrogen receptor ER-positive human epidermal growth factor receptor 2 HER2-negative advanced breast cancer is a cyclin-dependent kinase 4 and 6 CDK4-6 inhibitor plus endocrine therapy.

However, in patients with disease progression during first-line CDK4-6 inhibitor therapy, effective treatment options remain limited, and responses to subsequent endocrine-based therapies are often not durable.

Geradestrin and Everolimus target the ER pathway and the mTOR signaling pathway, respectively, and these pathways are implicated in endocrine therapy resistance.

In this Phase III trial, 373 patients with ER-positive HER2-negative advanced breast cancer who had disease progression or recurrence after receipt of a CDK4-6 inhibitor were plus endocrine therapy, were assigned to receive an all-oral giridestrant plus everolimus regimen or standard endocrine therapy, such as eczemestane, fulvestrant, or tamoxifen, plus everolimus.

An all-oral giridestrant everolimus regimen led to significantly longer progression-free survival than standard endocrine therapy everolimus, mainly in patients with ESR1-mutated tumors.

Telex agreed to acquire ITM, a producer of medical isotopes that also owns ITM11, an investigational lutetium-177 infusion for neuroendocrine tumors of the gut and pancreas.

In its phase three compete trial, ITM11 improved progression-free survival over Everolimus.

That wasn't a comparison with Lutathera, and ETM11 is a separate program from Bravnetza.

For Telex, the deal is about what comes after imaging.

Right.

I'm looking at Kim's 2025 Everolimus trial.

It's a phase two randomized placebo controlled crossover design.

They enrolled 23 patients with persistent FCD2 seizures who had already failed surgery and 21 completed both 12 week periods.

But honestly, the results are tough to parse.

They are very challenging.

The primaries and powder comparison looking at who achieved a significant reduction in seizures was 24% on Everolimus versus 19% on placebo.

The p-value was 0.66.

So, Joyce, you also see a bunch of papers and, again, ongoing trials combining L-acestrin.

Here's one study that's going to combine with Everolimus, another with Abema, another with capecitabine.

And, of course, we're going to talk in a second about Ember 3.

Any comments about the idea of these SIRD combinations, Joyce, and where you see that heading?

It's quickly broken down in the digestive tract.

So that's why companies have created Sirolimus or Everolimus, because those are forms of rapamycin that can actually be absorbed.

And we chose serolimus because it's more selective towards mTOR complex 1, whereas everolimus seems to be equally split between mTOR complex 1 and mTOR complex 2.

And the lifespan extension effects are thought to be because of mTOR complex 1 rather than mTOR complex 2.

And so what you're looking at, the hazard ratios, you're looking at how long it takes for these people to get to that endpoint.

And this is where the treatment group, the Everolimus group, looks better, right? Hazard ratio 0.43, well, less than one.

And so then you have to consider, okay, is that benefit over the time course of the study worth the downside of this medication, toxicity, financial toxicity, whatever?

That's a great point.

239 minus 60 is 179.

And we have 177, which is actually only two people censored on the control arm.

So what's happening in this study? New drug, costly, toxic drug paired with Everolimus.

7% of people are censored at time 0.1.