Agents or Regimens Moving from Metastatic to Early Stage

A review of the potential agents or regimens that Allison Butts, PharmD, BCOP, is looking forward to seeing transition from metastatic management to the early stage setting.

Jacob Kettle, PharmD, BCOP: Moving forward, we already touched on this a bit. Is there any molecule out there that’s currently in the metastatic space—a regimen or something out there—that you suspect may lead to new developments in the early stage breast cancer space?

Allison Butts, PharmD, BCOP: There are a couple of other drugs that are currently not approved adjuvantly. If we look at trastuzumab deruxtecan, which is 1 of our newer approved agents that I mentioned previously, I certainly believe we’ll see results coming out in the future about the role of that drug in patients with residual disease. Likewise, we’ve seen a number of trials that tried to look at the targeted therapy and the antibody-drug conjugates combined with pertuzumab to see if there is any benefit to that regimen, whether it’s toxicity or efficacy. So far, we’ve not seen that come to fruition.

Jacob Kettle, PharmD, BCOP: Is that the KAITLIN trial you’re referring to there?

Allison Butts, PharmD, BCOP: Yes.

Jacob Kettle, PharmD, BCOP: Do you want to expand upon those results briefly?

Allison Butts, PharmD, BCOP: Sure. As I said, the KAITLIN trial looked at using the ado-trastuzumab emtansine [T-DM1] in combination with pertuzumab versus trastuzumab-pertuzumab and a taxane after these patients received the anthracycline therapy as an adjuvant treatment for high-risk HER2 [human epidermal growth factor receptor 2]—positive breast cancer. Based on these results, we did not see any significant benefit to using T-DM1 [trastuzumab emtansine] in place of the trastuzumab-taxane combination. In terms of toxicities, more patients discontinued the T-DM1 [trastuzumab emtansine] arm because of adverse effects than the standard-of-care taxane-trastuzumab arm, which was interesting. That’s 1 of the multiple trials that have tried to look at using pertuzumab in combination with these combo therapies.

Jacob Kettle, PharmD, BCOP: We’ve seen that, if you’re looking at the neoadjuvant space, like a couple of these trials we’ve looked at, you’re scraping some very thin margins. Although we need to improve on it, it’s hard to improve on something that works so well, just like trastuzumab. That’s where I think of all these new things we talked about. The KATHERINE study is again what stands out because that’s a different treatment approach. It’s not just an additive or slight tweak to a regimen. It’s a unique and different approach to treatment.

Allison Butts, PharmD, BCOP: To go back to your original question about other potential therapies moving from metastatic into the curative intent setting, we’re going to see parallels to the ExteNET trial. Perhaps with tucatinib, 1 of our newer TKIs [tyrosine kinase inhibitors]—trying to use that to potentially prevent patients from brain metastases. Perhaps that’s something else coming down the line as well.