SABCS 2020: Other Oral Therapies for Breast Cancer

EP: 1.Breast Cancer Treatment: Year in Review

EP: 2.SABCS 2020: CDK4/6 Inhibitors for Breast Cancer

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EP: 3.SABCS 2020: Other Oral Therapies for Breast Cancer

EP: 4.SABCS 2020: AKT Inhibitors for TNBC

EP: 5.Precision Medicine in Breast Cancer

Adam M. Brufsky, MD, PhD: We’ll now talk about 3 more abstracts that are interesting.

With the first abstract, I’ve been involved with the team at Odonate Therapeutics for a long time. I’m sure that they probably talk to you a lot; they talk to a lot of us. The CONTESSA trial is pretty cool. I like the idea of an oral taxane. The alopecia is minimal. There is something that I didn’t like about this design, and I told this to them, as I’m sure you did, when they all talked to us a couple years ago.

Basically, when you’re on hormonal therapy and progress, we normally give you capecitabine. In this case, all they did in the CONTESSA trial was add a single dose of tesetaxel, I think it’s 27 mg/m2, every 3 weeks. The adverse effect profile was basically what you would expect: a bit more neutropenia and a bit of neuropathy, but not much more. It was dominated more than anything by the capecitabine effects. It apparently has some impact. We don’t know the results. They just showed some PFS [progression-free survival] and the usual signs by press release. I’m going to be curious to see those data. I think that’s going to be a big trial to see. What do you think of that trial?

Erika P. Hamilton, MD: I also think it’s interesting. It’s interesting that the oral taxanes have a bit of a different adverse effect profile, as you mentioned, compared to an IV [intravenous] taxane, so that’s important from a hair loss and a neuropathy standpoint.

The other thing that 2020 has taught us is about COVID-19 [coronavirus disease 2019]. It is attractive to have more oral therapies that patients can take on their own at home with some local laboratory monitoring or symptom checks. Even telemedicine is attractive in a time where, for some patients, it’s hard to get into the clinic, and it’s risky for others.

Adam M. Brufsky, MD, PhD: I agree. It’s always good to have that. To change gears for a second, I can never pronounce it, but they have Phesgo [pertuzumab, trastuzumab, hyaluronidase], or whatever they call it. It’s a combination of pertuzumab and trastuzumab as a subcutaneous formulation that can potentially keep people out of the hospital. Have you started using that at all [at Sarah Cannon Research Institute, Tennessee Oncology]?

Erika P. Hamilton, MD: No, have you?

Adam M. Brufsky, MD, PhD: No, I haven’t. We [at the University of Pittsburg] just received it. For now, we’re trying to figure out how to integrate it into our practice. Apparently, there are people who have started using it: I know Mark Pegram, MD, uses it a lot now at Stanford [Health Care], and he loves it. He says that patients like it, and they don’t mind it in clinical practice. They have this thing going on: they’re doing a quasi-trial where they have visiting nurses deliver it to patients within their homes. This is all big, it goes back to COVID-19, which is basically why they’re doing it.

The other thing to go on at the San Antonio [Breast Cancer Symposium], it’s in the same session. It’s GS402 [general session 402], this whole thing with entinostat. This is an ECOG [Eastern Cooperative Oncology Group] study for which Denise Yardley, MD, was the PI [primary investigator], apparently. It was weird that it was a randomized phase 2 trial of this HDAC [histone deacetylase] inhibitor with or without exemestane. That basically showed no PFS, but there was a survival benefit. It always got me scratching my head, but it led to this phase 3 trial, and I was surprised that it was negative, especially because they had that phase 2 data that looked so good. Do you have any thoughts on that study?

Erika P. Hamilton, MD: I agree. I feel like entinostat has been around for a long time. It’s resurrecting here in a result. It’s disappointing. We’ve certainly given it across multiple trials in a few different ways, and it looks like it’s had some activity. It certainly adds a bit of toxicity to the regimen that it’s given with, but I’m eager to see the entire results.

Adam M. Brufsky, MD, PhD: It was a big deal with the Stand Up to Cancer program. They did vorinostat and 5 days of azacitidine in a phase 2 trial in leukemia and breast cancer. It was this big Stand Up to Cancer study, and they got $10 million for it or something like that, and there were all these biomarkers that were done with it. It never worked; the phase 2 study never took off.

That’s why, when I saw this huge trial around the time when Denise presented that data from ECOG, we said, “Ok. Maybe it will work,” but it didn’t. Again, we have to learn from our failure here. That is going to be an interesting thing: why did it fail? Were there subgroups in which it worked? We’ll have to see.

Transcript edited for clarity.