Top News at the 2019 SABCS — Heard in the Halls

Jack Goodpasture: Welcome to San Antonio Breast Cancer Conference, I’m Jack Goodpasture. I’m the senior director of medical affairs at Eli Lilly & Company, Lilly Oncology, and I’m excited to be here.

Jamie DePolo: So could you tell us a little bit, what are some of the biggest things patients need to know about that were discussed here at 2019 San Antonio Breast Cancer Symposium?

Jack Goodpasture: Well, San Antonio always delivers great information, great new information. You can always gauge interest in scientific disclosure by how many cameras go up in the room when the disclosures are happening. I think where I saw a lot of cameras go up this week were in the HER2-positive metastatic space.

There were two disclosures in particular that I think gathered a lot of attention. The first one is the result of a study called HER2CLIMB. It was looking at an investigational molecule called tucatinib in combination with a HER2 targeted therapy and chemo versus placebo in combination with a HER2 targeted therapy and chemo.

What was really interesting about this study is it also included patients with brain metastasis. So of a lot of interest to patients with that diagnosis. This study looked at progression-free survival, overall survival, and then broke out that cohort of patients that had brain metastasis. Interestingly enough, the drug performed well across all of those variables including the patients who had brain mets. So that was exciting data, it’s an investigational molecule.

I think the second really interesting study in the HER2-positive space has to do with an investigational molecule by Daiichi Sankyo. We call it DS-8201, and it’s a drug that was looked at in patients who are also pre-treated. They were really looking for response rates here. They saw in that patient population really robust responses and really durable responses. So again, in the HER2-positive space, heavily pre-treated. These were third line types of patients. You’re seeing new therapies come along that are offering a benefit. So that’s certainly exciting for patients.

Moving on, the class of drugs that’s received a lot of attention this year, not just here in San Antonio but throughout the year, are what we call the CDK4/6 inhibitors. These are drugs like Verzenio, Ibrance, Kisqali. Going all the way back to ASCO of this year, you saw Kisqali disclose some positive overall survival data. Then at ESMO, Verzenio demonstrated a 9.5 month overall survival benefit in a patient population that had previously been on endocrine therapy. So these are patients that had progressed through endocrine therapy and a 9.5 month overall survival benefit. Then the MONALEESA-3 trial, another trial for Kisqali, demonstrated overall survival.

So there’s been a lot of excitement around these molecules this year. As you come into San Antonio what you’re seeing is further understanding of how the drugs are performing in a variety of places. I’ll point out a couple of things.

For abemaciclib, or Verzenio, that MONARCH 2 study, which I mentioned earlier, are patients who had Verzenio plus fulvestrant or placebo plus fulvestrant after having progressed on prior endocrine therapy. With that 9.5 months survival benefit, some of the questions that come up are how did the subgroups of patients perform? We took a look at patients who have previously identified prognostic factors that would confer a less favorable prognosis. So things that might make you think that that patient’s presentation would be less likely to do well.

Jamie DePolo: What kind of things are those?

Jack Goodpasture: I’ll point them out. So some things like liver metastasis or if the tumor has a really high grade. There was previous work that’s been done that identified that those things may confer a poorer prognosis. In this analysis — it’s an exploratory analysis in that MONARCH 2 overall survival data — the encouraging thing to see was that the drug performed very consistently no matter what the poor prognostic subtype was. So again, just adding to the body of knowledge there.

We also took a look in the MONARCH 3 patient population. So these are patients who are what we would call first-line metastatic. A really interesting exploratory analysis done there. So this was Verzenio in combination with an aromatase inhibitor in the frontline setting. We were looking at progression-free survival as a primary endpoint in that study. One of the questions that comes up often is breast cancer comes in a lot of different varieties, so were there genomic alterations available in those patients that we could detect, and how did the drug perform there as well?

We were excited to present here. We took a look at circulating tumor DNA, so in the blood, sequenced it for over 70 different genomic alterations. And what was interesting was we saw, again, consistent performance in the Verzenio plus AI group in terms of those genomic subtypes. The drug still performed really well, consistent with the intent-to-treat population. So again, we’re seeing more and more data come out that just speaks to how reliable and consistent these drugs are, which is really exciting for patients, for sure, and really informative for their healthcare practitioners.

Editor’s Note: On April 17, 2020, the FDA approved Tukysa (chemical name: tucatinib) in combination with Herceptin (chemical name: trastuzumab) and Xeloda (chemical name: capecitabine) to treat metastatic HER2-positive breast cancer or locally-advanced HER2-positive disease that can’t be completely removed with surgery, after the cancer has been treated with at least one anti-HER2 medicine.