Practical considerations for implementation of HER2-targeted therapies | S14E2

Uh-

Uh-Mm-hmm.

David, let's now discuss the adverse events and how, uh, we manage them.

ADCs and TKIs have, uh, different toxicity profiles.

ADCs, uh, may, uh, cause, uh, uh, adverse events, uncommon, uh, such as, uh, uh, ILD, pneumonitis, uh, uh, gastrointestinal effects and TKI, uh, TKIs are associated with, uh, cases of hepatotoxicity and also ILD and, uh, gastrointestinal effects.

So how should, uh, these toxicities, uh, be monitored and managed during, uh, the treatment of patients with HER2 mutations?

So I would say with the TKI, as you said, the most frequent type of toxicity is GI toxicity and skin toxicity.

And particularly, you have nearly, uh, between, uh, fifty to eighty percent of, uh, GI toxicity in term of diarrhea.

So you need to manage and probably anticipate in some patient, and those adaptation level should be something, uh, that can clearly improve the tolerability of the treatment.

The rash, paronychia is something also quite frequent, uh, with the HER2 TKI.

I would say much more frequent, uh, particularly with savolitinib if you compare to zongepanib, notably in term of GI toxicity.

So I would say probably a better tolerability, uh, with zongepanib in comparison to savolitinib and directly, uh, this is the most frequent toxicity.

Just look at the liver toxicity also, just something to monitor.

So I would say w-we are used to adapt this type of toxicity as we have some time with the EGFR TKI.

So the GI, skin toxicity, and the liver toxicity, and in nearly, I would say, ten to f-fifteen percent of patient who might need to have a dose reduction level, and generally, uh, you have a better tolerability of the treatment.

So it's not a major issue, but anticipate the GI toxicity.

And with the ADC, uh, the most frequent toxicity, you have the toxicity of chemotherapy because you have the toxicity of the payload.

It's topo one isomerase inhibitor.

So you need anticipate also the GI hematological toxicity.

There is no treatment of prevention to give.

It's mainly grade one, grade two toxicity.

So in my experiences, it's not really, uh, an issue to manage this type of toxicity.

The most important and concern of toxicity is the ILD toxicity with trastuzumab deruxtecan.

You know, with the higher dose level, it was nearly twenty-five percent of patient.

Nowadays, at five point four milligrams per kg, it's around ten percent of ILD.