Overview of Treatment Options in HER2+ Metastatic Breast Cancer


Shared insight on the treatment armamentarium for patients diagnosed with HER2+ metastatic breast cancer.


Andrew Seidman, MD: It’s been about a decade since the publication of CLEOPATRA, and taxane/trastuzumab/pertuzumab has really kind of been a mainstay of treatment for quite a while. Tiffany, are there patients where you wouldn’t lead with paclitaxel or docetaxel and HP [trastuzumab, pertuzumab]?

Tiffany Traina, MD: Great question. As you said, this is still our mainstay first-line treatment approach for HER2-positive metastatic breast cancer. [Participants in] CLEOPATRA had an impressive overall survival [OS]. That had docetaxel as its backbone chemotherapy, but we’ve also seen paclitaxel/trastuzumab/pertuzumab as a reasonable option and supported in NCCN [National Comprehensive Cancer Network] guidelines….

Great regimen, our standard of care. Where I give some pause is in my patients who unfortunately had perhaps neoadjuvant or adjuvant taxane and have had a really short disease-free interval.

Andrew Seidman, MD: Five months, 10 months?

Tiffany Traina, MD: Less than 6 months, even less than a year. I’m somewhat concerned.

Andrew Seidman, MD: So what do you do in those really refractory patients who’ve had a taxane in the adjuvant or neoadjuvant setting, and it’s 6 months out and their cancer has come back?

Tiffany Traina, MD: Fortunately, we’re not seeing this as much as we used to as a result of our impressive agents available in the early stage setting. But I think that’s an opportunity for antibody drug conjugates [ADCs] really, which we have for HER2-positive disease. Consider drugs such as T-DM1 [trastuzumab emtansine], which had been second line, if somebody is recurring so quickly on their early stage trastuzumab/pertuzumab. Maybe move up those ADCs earlier.

Andrew Seidman, MD: So VK, the EMILIA trial really kind of set the standard for what to do when you’ve progressed despite first-line taxane/trastuzumab. Can you just remind us about EMILIA and tell us why it may not be as relevant today.

Vijayakrishna Gadi, MD, PhD: That was a molecule, you might recall. What is it called, lapatinib? So lapatinib was our first-in-class, small-molecule inhibitor available for HER2-positive disease. In retrospect, [it’s] probably a sloppy inhibitor, it hits HER1, HER2, some other kinases, but in combination with capecitabine was safe enough to be challenged in that second-line setting. It won that war at that time. But we all recognize that there were still a lot of gaps. [Patients] would still progress relatively soon, and there was a need to develop additional agents into that space. The first drug to take that mantle was T-DM1, trastuzumab and emtansine. And then more recently, we got this really exciting data with trastuzumab deruxtecan in that space. A randomized clinical trial comparing trastuzumab deruxtecan with T-DM1 [trastuzumab emtansine], that study had 22 zeros in the P value. Do you know the last time we saw a drug approval trial with 22 zeros?

Andrew Seidman, MD: That was probably adjuvant Herceptin [trastuzumab] data.

Vijayakrishna Gadi, MD, PhD: It was when we added Rituxan [rituximab] and CHOP [cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone]. It’s been awhile.

In this trial, clearly we’ve got superior progression-free survival data, a hint of OS already, although the events are still occurring so we’ll know what that looks like [in the future]. At this meeting we learned that depending on how you analyze this safety data you could make the case that given the exposure time [patients] who are benefiting from a drug are going to be on it for longer. When you amortize the toxicity over that timeframe, you can create ratios that actually suggest that T-DM1 was actually more toxic in some scenarios and some cases. So we’re getting comfortable with that drug, and I think it’s clearly now the preferred agent for a lot of patients in that second-line setting. I’m not touching on tucatinib because I know we’re going to get there.

Andrew Seidman, MD: We’re absolutely going to get there. We have new data and we also have NCCN guideline updates. Stephanie…tell me about how NCCN guidelines impact your practice, your patients, reimbursement, all of the above?

Stephanie Graff, MD: The NCCN does a great job of updating the guidelines in real time. We get numerous updates a year in between NCCN guidelines and, honestly, FDA package inserts, which I think are treasure trove of information, and ASCO [American Society of Clinical Oncology] guidelines. I feel as oncologists we have wealth of information that can really support our clinical practice both with patient decision-making and with payers. All of that information gets updated real time in a way that drives decision-making and is reflective of these changes that we’re seeing coming out of conferences, big publication updates, and [INAUDIBLE]. I think that keeping up-to-date with sources is really relevant for a practice. I don’t know that I am trolling NCCN guidelines nightly but I think that it’s definitely a ready resource.

Transcript edited for clarity.

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