Transcript

Dear colleagues, my name is Solange Peters. I'm working as medical oncologist in Lausanne in Switzerland. I am the head of medical oncology as well as the thoracic unit at the university hospital in the city of the Lausanne.

One of the interesting trials I'd like to discuss with you, which to me, is probably one of the most interesting, because it's about a completely new strategy and really innovation for a subset of all patients, is about this drug which has a name which nobody can pronounce, trastuzumab deruxtecan, which is targeting HER2.

It's targeting HER2 as an antibody drug conjugate with very specific property, a payload which is a very active chemotherapy component, with several molecules of this chemo being conjugated to the antibody, and an antibody targeting the extra-membranous part of the HER2 protein.

DESTINY trial will evaluate this drug in HER2-positive disease in NSCLC. Be careful when we speak about HER2 alteration. It can be just an overexpression or an amplification; remember breast cancer. Sometimes, HER2 is amplified. Sometimes, it's overexpressed in lung cancer, too (more rarely, but it also happens).

HER2 can be mutated. Mutation have very often insertions found in the exon 20 of the gene.

So this drug, the trastuzumab deruxtecan, will be tested in overexpression, as well as in mutated HER2. The data we have been seeing at the ASCO meeting was the mutated cohort. Where do we come from?

We do come from, I would say, a long way. I participated in many of these trials, with trials aiming at targeting these HER2 mutations. Considering it as a potential driver corresponding or equivalent to EGFR, iKRAS, and RET.

Probably the driver force is a little bit weaker. And basically, what we have been testing until now was slightly disappointing. We've been trying afatinib, dacomitinib, with a response rate around 10% or even lower.

We've been testing TDM1 or TDMI, I did test it in overexpression. Colleagues from the US centers tested it in mutated HER2, with some, a bit more promising response rate, not for overexpression, but for mutated, around 40%, but a very small number of patients.

Last, but not least, we have some data with poziotinib and pyrotinib, which again, a very small subset of patients, maybe a bit more promising, but remember that poziotinib has some toxicities that have to be taken into account.

So we start from there. Small series, and some disappointment, I must say. And DESTINY, suddenly, this phase 2 has 42 patients, which is from far, the largest sample size we have. And also, a very interesting response rate of 60+, 61%.

It has also been showing, and of course, in this trial, this phase 2, it was not front-line, it was in later lines of HER2 mutation, like it is supposed to be done when you test a new compound.

What was interesting is this PFS. This PFS was shown being 14 months. I think there, it's extremely interesting to consider this drug as being a new challenger for front-line therapy.

I think it reaches the numerical values for PFS and response rate which might allow this transfer, this challenge against chemo on front-line. It deserves further evaluation; first, of course, expanding the sample size, and maybe thinking about moving it ahead to front-line.

Of course, one topic which was very rapidly addressed in this presentation is the potential ILD, inflammatory lung disease, that everybody has to know about, which was already described in other disease entity and has that be further described.

It looked like in the slide to be absolutely manageable, but I think the way to manage it, the way to detect it, and how we can potentially prevent it needs to be further described.

On the other hand, there's something in favor of moving front-line here is probably, as we have seen with all targeted therapy, usually front-line result does slightly better. Also, because the safety pattern is always more obvious when you are front-line, because you can treat any potential cumulative toxicit (I'm thinking about immunotherapy; we all know that immunotherapy can add some toxicity when it was given previously)

So amazing data set, very happy to see it, and I am looking forward to see more data with this compound.