PD-L1

And in 2026, you need to have a multidisciplinary discussion to go over the perioperative systemic therapy approaches as well as the adjuvant approaches.

You need to be checking ALK, EGFR, PD-L1 as these do tailored treatment approaches in this group.

If EGFR positive, stage 1b to 3a, you're going to talk about surgery followed by adjuvant chemo.

And then you're going to think about three years of adjuvant osomertinib based on the ADORA trial.

For smaller tumors, you can get away with TC.

So that's docetaxel cyclophosphamide.

For larger tumors more than 2 centimeters or positive lymph nodes, you're going to do your Keynote 522 regimen and add PEMBRO perioperatively regardless of the PD-L1 status.

And then for residual disease, you're going to give capecitabine based on the CREATE-X trial.

For a long time, I mentioned that our treatment for triple negative breast cancer was just chemotherapy.

Then we got into that PD-L1 story and we found that for some patients, we could also give immunotherapy.

And then that's really been our mainstay of treatment.

And then these new drugs came out.

TROP2 is just the protein that they target.

And they both beat chemotherapy.

And for patients who have positive PD-L1, the combination with sasituzumab and immunotherapy also beat the combination of chemo and immunotherapy.

And I think this has really changed the game immensely because as I'm sure you guys may have seen, there was some very sad data that came out about triple negative breast cancer a few months ago.

So we have a strong translational part on this because from the clinical standpoint, we do not see any major predictor for the benefit of NEVO versus Regime Gemsis alone.

If we consider the clinical stage, PD-L1 status or the renal function, what we collected is a huge body of translational research pointed to the ctDNA by using the signatory assay.

which was evaluated at baseline cycle one day one and at the end of the new adjuvant part, the cycle four day one.

And we actually saw that the clearance of the cDNA, the negativity baseline of the cDNA, they both impacted quite a lot on the prognosis of the patients.

A Phase III trial tested it as first-line treatment with Keytruda.

The patients had non-squamous lung cancer that was PD-L1- without EGFR or ALK alterations.

Keytruda was in both arms, and the comparison arm paired it with pemetrexed and platinum chemotherapy.

That makes the trial's questions specific.

So it makes sense scientifically, I think, to consider all of them.

Now, this question gets into the overall survival advantage with B96 and considering it in a patient with PD-L1-negative disease.

And, you know, I think we obviously are label-driven, and we practice according to the label, but I think that, you know, you just said that ITT population demonstrated overall survival benefits, so certainly it might be something to consider in a PD-L1-negative patient, but, you know, looking at all other options, considering Alex's option and making that balance.

Godfried, what about pre-existing autoimmune conditions? Are there any specific conditions that cause you to withhold the use of checkpoint inhibition? And especially, I think, something that comes up a lot, not a lot, but questions that we get asked from other providers is around solid organ transplant.

Like, what do you do there?

In the metastatic setting, we actually have two antibody drug conjugates approved.

One is in combination with immunotherapy for tumors at high have a specific biomarker that predicts benefit from immunotherapy known as PD-L1.

And so, yes, so we have two ADCs approved now in triple negative breast cancer.

Currently, there are very important studies that are ongoing looking at the addition using ADCs for patients who did not achieve a complete response after neoadjuvant chemoimmunotherapy.

And now, with almost five years of follow-up, we are so glad to confirm the long-sustained benefit from atezolizumab when we put on top of chemotherapy plapebacizumab.

And something else, I mean, we enroll all camera population, but we run an exploratory analysis, and we can say that, you know, considering the nature of exploratory analysis, that all patients seem to benefit from atesolizumab regardless of PD-L1 status.

So, with all this data, NCCN has listed the VET-CC regimen as a preferred first-line therapy irrespective of the PD-L1 status.

Yeah, these were amazing data, so reassuring.

So I guess my question for you is, are you using this regimen for everybody or the PD-L1 negative?

Thank you for this question.

So I'm absolutely convinced that patients with cervical cancer should receive immunotherapy.

So what we do in our daily activity is those patients whose tumor has CPS, Since pembrolizumab is approved, we treat the patient with pembrolizumab and chemoplasma in a web.