Data Updates and Ongoing Trials in the HER2+ Adjuvant Space

Transcript:

Sara Hurvitz, MD: Before we move on to some newer drugs that are being looked at, I want to ask you, Virginia, I don’t know if you saw there was at ASCO [American Society of Clinical Oncology Annual Meeting], the long-term follow up from ShortHER [trial], which is 9 weeks of trastuzumab vs a year of trastuzumab randomized study. It did not meet its non-inferiority end point at the first reporting, and now they have 9 or 10 years of follow up. It was very interesting. It really looked like the hazard ratio was about 1.06. It still didn’t meet that non-inferiority end point, but boy did those curves look like they were right on top of each other. But when they broke it out, because you were talking about stage I and deescalating and when you use trastuzumab or not, but when they broke it out according to risk and stage, those higher stage patients clearly needed the full year vs the lower stage. [They] might be OK with 9 weeks. Are you going to do this in clinical practice? Are there situations where you don’t give the full year based on data like these?

Virginia G. Kaklamani, MD, DSc: I think there are. Especially if we have patients that are just really tired with our therapy. This all started years ago with the FinHer trial. The Finnish government said we don’t have a year worth of Herceptin to give patients and we can only give 9 weeks. Prove to us that 9 weeks is better than nothing. And they did. Since then, we’ve had multiple trials, mostly looking at 6 months.

And this non-inferiority design is very tricky because somebody has to decide that 2% or 3% is OK or is not OK. And we’re not statisticians. We treat patients and we talk to patients. We have to explain to them what this really means and is this 2% OK for them or not. And so, I don’t know that I would do 9 weeks, but I would definitely do 6 months, especially for my lower risk patients.

Sara Hurvitz, MD: Good. In resource restricted areas these type of data are very important when ‘ thinking about the cost of medicine and access. All right, Heather, we’re going to round up this section and talk a little bit about recent data updates in the adjuvant HER2+ early [breast cancer] space. Just take me through some things you’d like to talk about here.

Heather McArthur, MD: Sure. There are a lot of really exciting clinical trials that are ongoing in this space. It really underscores our efforts at the current time to really tailor treatment recommendations based on things like pathologic complete response. The CompassHER2-pCR residual disease study we’ve already mentioned. Just as a reminder that’s taken patients who are at high risk of recurrence because they haven’t achieved a pathologic complete response and randomizing them to the standard of care, which is T-DM1 [trastuzumab emtansine] based on the KATHERINE data vs T-DM1 plus tucatinib. Tucatinib of course having important impact based on the HER2CLIMB data and became an FDA-approved regimen in that space. So that’s been a very popular clinical trial that’s been enrolling very rapidly.

There are also a number of other really interesting clinical trials going on. It’s a really exciting drug development space actually. There is a study based in Canada called the KAN-HER2 MRD study. This is a study looking at molecular residual disease, MRD. What they’re doing in this study is they’re taking that high-risk population with residual disease who are receiving T-DM1 per standard of care, and they’re looking at ctDNA [circulating tumor DNA] after 2 to 6 cycles of T-DM1. Patients who have residual molecular disease by that assay, they’re getting the addition of neratinib. So that’s a really interesting concept and is very much aligned with our ongoing interest in looking at liquid biopsies as a potential platform to inform downstream decision-making. So that study is ongoing.

There’s also a really exciting vaccine space. HER2-directed vaccines have long been an area of interest. We haven’t really had a lot of success in that space to date, but there is some recent data that’s actually really compelling looking at a HER2-directed peptide, GLSI-100, HLA-A*02 and HER2+ disease. They get 6 injections in the adjuvant space for residual disease. And the early phase data with this vaccine is actually incredibly exciting. So we’re opening that study ourselves. It’s called the FLAMINGO-01 study. The data so far is really compelling. I think it’s really an exciting space.

Sara Hurvitz, MD: I really agree. I think all of these drugs that are being looked at in the adjuvant setting, as you mentioned, tucatinib and neratinib, and using the minimal amount of residual disease to help guide what we do. [With] immune-based therapy vaccines and T-DXd [trastuzumab deruxtecan], we’re going to have a lot to talk about in a few years at this type of a panel discussion. Absolutely.

Transcript edited for clarity.