Escalation or Deescalation of Therapy in Early-Stage HER2+ Breast Cancer

Transcript:
Andrew Seidman, MD: Bill, there have been some European attempts at de-escalation strategies, [such as] the ADAPT trial that Nadia Harbeck [MD, PhD] presented at ASCO [American Society of Clinical Oncology annual meeting] last year, the DECRESCENDO study which is still ongoing from the Breast International Group. Can you tell us a little bit about those efforts?

William Gradishar, MD: Sure. The ADAPT trial was an effort to actually figure out if you could [do] without chemotherapy. It was a combination of dual HER2 targeting with a taxane or not, meaning no taxane. It involved a fairly broad group of patients with large tumors all the way up to I think T4, T1 to T4 and then 0 to N3. The effort was to try to determine if you could achieve a PCR [pathologic complete response] rate in the absence of chemotherapy that approached what you would get with chemotherapy. Unfortunately, it did not. At the present time…until we have a better marker to define who can avoid chemotherapy in a preoperative setting, you would use chemotherapy with HER2 targeting.

Andrew Seidman, MD: Luca Gianni, [MD], from NeoSphere, might have said, “I told you so.”

William Gradishar, MD: If you only knew who those patients were. The DECRESCENDO study from the Jules Bordet Institute [in Anderlecht, Belgium] is looking at taxane combined with Phesgo [pertuzumab, trastuzumab, hyaluronidase] in patients who achieve a PCR and comparing that with just Phesgo [pertuzumab, trastuzumab, hyaluronidase] itself or switching to T-DM1 [trastuzumab emtansine] if they did not achieve a PCR. The goal of that trial is to see if you can approach an optimal event free survival of upwards of 90%. If that were achieved, then that may be a rationale for saying it’s comparable to more conventional chemotherapy approaches.

Andrew Seidman, MD: We participated in COMPASSHER2, and [we] have had patients who’ve gone down the path and done wonderfully, then after 12 weeks of weekly paclitaxel and HP [trastuzumab, pertuzumab] aren’t quite where we want them to be. They still have significant palpable disease. Do you tell the patient, “Let’s go to surgery and we’ll deal with whatever we deal with after, when I have your pathology report in front of me,” or are you more inclined to say “Let’s give AC [doxorubicin, cyclophosphamide] or some other therapy preoperatively,” if you’re not quite there yet?

Tiffany Traina, MD: It’s a great question. I think it’s a long discussion with our patients, because [although] pathCR [pathological complete response] is very satisfying and prognostic, I think we have to really look at the data that we have and think about event-free survival as a really important end point and overall survival as our long-term aspiration. There’s value in proving someone has [not achieved] pathCR after that THP [paclitaxel, trastuzumab, pertuzumab]. Even with a biopsy, you know you have disease there and introduce some additional neoadjuvant therapy to try to achieve pathCR downstage or get to breast conservation. Then knowing that, we readdress what to do in the adjuvant setting, a la KATHERINE, if you still have residual disease there.

Andrew Seidman, MD: So if you’re really unhappy with the 12-week experience with taxane, HP [trastuzumab, pertuzumab], you don’t necessarily stop there. Any other thoughts on this?

Vijayakrishna Gadi, MD, PhD: Just a couple of things. Philosophically, we need to set up our patients for these expectations. In other diseases, we know it’s a 2-year journey, but we’ve sort of made it a 6-month or 3-month journey in this cancer. But now that we understand there are patients who are going to have very different outcomes, preparing our patients to be ready for a 2-year journey is probably something we need to start doing more of. And I have a question because it has kind of come up a few times. Are you ever tempted to look at ctDNA [circulating tumor DNA] to make a decision?

William Gradishar, MD: No.

Tiffany Traina, MD: No.

Vijayakrishna Gadi, MD, PhD: [Patients] have been asking me about that.

Andrew Seidman, MD: I actually do want to go off the farm a little bit and ask you a question that came to mind. We’re constantly talking about escalation and de-escalation, are there patients out there who should be treated as per May 16, 2005, when we saw the first adjuvant trastuzumab data patient. Is there anyone who is appropriate for TCH [docetaxel, carboplatin, trastuzumab] or ACTH [doxorubicin, cyclophosphamide, paclitaxel, and trastuzumab], or does everyone needs to get ACTHP [doxorubicin, cyclophosphamide, paclitaxel, trastuzumab, pertuzumab], TCHP [docetaxel, carboplatin, trastuzumab, pertuzumab], or de-escalation therapy a la [Dr Sara] Tolaney.

Stephanie Graff, MD: I still do give inflammatory breast cancer an anthracycline. As far as escalation therapy goes, I think it’s important to identify that inflammatory cancer is just a different beast.

Andrew Seidman, MD: But you would omit pertuzumab in that patient?

Stephanie Graff, MD: Maybe not.

Andrew Seidman, MD: For myself, there are some patients who, I think, were underrepresented in the ATEMPT trial. Younger patients with T2, N0 disease represented 10% or [approximately] 40 patients. There are some of those patients I’m not so sure I want to escalate; I’m not quite comfortable, I want to deescalate. Maybe I’m subsetting too much.

Transcript edited for clarity.