Trastuzumab emtansine

The evidence was already public.

Destiny Breast O5 was the phase 3 that compared NHER2 with TDM1 in that high-risk population with disease remaining after pre-surgery treatment.

Prostate cancer brought a U.S. label expansion into an earlier treatment setting.

On October 26, the FDA approved Pfizer's Telzena with Xtandi for adults with metastatic prostate cancer that's either untreated with, or still sensitive to, androgen pathway drugs.

So you're adding pertuzumab.

If there is residual disease after neoadjuvant HER2 therapy, The new category one is TDXD or trastuzumab duroxacan, but in the boards, at least when we took them in the last few years, it might not be updated yet, is TDM1 based on the Catherine trial.

And then for TDXD, always remember interstitial lung disease.

I'm sure there'll be some questions on that.

If there is residual disease after neoadjuvant HER2 therapy, the new category one is TDXD or trastuzumab duroxacan.

But in the boards, at least when we took them in the last few years, it might not be updated yet, is TDM1 based on the Catherine trial.

And then for TDXD, always remember interstitial lung disease.

I'm sure there'll be some questions on that.

Um, and we have it available and with a median PFS of 29 months in the second line.

Um, now, um, who I do consider, um, TDXC plus pertuzumab for, for my first line patients are certainly patients that are recurrent and maybe they're recurrent after, you know, trastuzumab, pertuzumab, maybe they had adjuvant TDM1, you know, you're not really going to want to re-challenge a patient like that with a taxane, especially if it's within short order.

So certainly recurrent patients I'm considering TDXC and pertuzumab, um, TDXD performs incredibly well for patients with brain mets.

So for TDXD has really the highest intracranial response rates that we've ever seen.

So CNS penetration.

TDM1 is also an option.

Leads to LFT abnormalities, thrombocytopenia, neuropathy.

And then trastuzumab, lopatinib, and then also neratinib, capecitabine.

Clinically, I think that we have seen that it is absolutely possible to give an ADC after another ADC when we're switching the payload.

Um, and I think that, you know, our best evidence of this still comes predominantly from the breast cancer world, where, um, the HER2 targeting ADCs, for example, um, you know, trastuzumab deruxtecan when it had its, you know, uh, huge splash with the Destiny Breast-01 trial, all of those patients had been pre-previously treated with, um, TDM-1, and so a different HER2 targeting ADC.

And yet the, the activity of trastuzumab deruxtecan in this population of HER2 positive, uh, breast cancer was really striking.

And I think we're starting to see a similar story emerging in the ovarian cancer space with the folate receptor alpha targeting ADCs, where in those early phase trials we've seen that patients who have had mirvetuximab, um, and then are being challenged with a, uh... whose tumors are being challenged with a folate receptor alpha targeting ADC that has a Topo 1 inhibitor payload, that absolutely we are seeing activity in that setting.

They suggested a change in my, um, immunotherapy.

So I had a, I changed from Herceptin to Kadcyla.

Mm-hmm.

Um, and I've been on Kadcyla since.

So throughout this, I've continued to have this immunotherapy every three weeks.

Um, but yes, I started the Kadcyla after the surgery just to, you know, as a change to see if that affects it.

Yeah.

But the oncologist was sort of wondering whether, um, they're s- they're very, um, very much reliant on hormones, so that's when I started my, the Zoladex injections as well.

HER2 overexpressing, uh, non-small cell lung cancer for a tumor agnostic label in IHC three plus is approved in, uh, the US, Japan, and the EU.

For comparison, uh, there are other treatments available for HER2 altered non-small cell lung cancer, um, in particular TDM-1, which was tested at least in two phase two studies, and you can see the results here.

They are, let's say, in terms of progression-free survival, not as promising as trastuzumab deruxtecan, but median overall survivals, you can see they are in more or less the same ballpark.

And as alluded to by, uh, the previous speaker, there is a, uh, ADC developed in China that has also already some results in, uh, non-small cell lung cancer with HER2 overexpression as defined by immunohistochemistry three plus or in situ hybridization positive.