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Pertuzumab and Other Agents Continue Progress in HER2+ Breast Cancer

Danielle Bucco
Published: Tuesday, Jan 02, 2018

Adam M. Brufsky, MD, PhD
Adam M. Brufsky, MD, PhD
The adjuvant treatment landscape for patients with HER2-positive breast cancer continues to grow, particularly following the recent FDA approval of pertuzumab (Perjeta) in combination with trastuzumab (Herceptin) and chemotherapy, which was based on findings from the APHINITY trial.

In the phase III trial, the combination demonstrated a 3-year invasive disease-free survival (DFS) rate of 94.1%, which represented an 18% reduction in the risk of developing invasive disease or death. The benefit was more pronounced among higher-risk patients. The DFS rate for patients with node-positive disease was 92.0% with pertuzumab versus 90.2% with standard therapy.

In an interview with OncLive, Adam M. Brufsky, MD, PhD, a professor of medicine, associate chief of hematology/oncology, co-director of the Comprehensive Breast Care Center, associate director of clinical investigation, University of Pittsburgh, discussed the developing role of pertuzumab in HER2-positive breast cancer, as well as the impact of other agents in the field.

OncLive: Can you discuss the impact of pertuzumab on the treatment landscape for patients with HER2-positive breast cancer?

Brufsky: Many oncologists in the United States will treat patients with neoadjuvant chemotherapy. The reason we have done that is because it was the only setting in which pertuzumab was approved until recently. If we decide someone needs anti-HER2 therapy and chemotherapy, we generally will give them either docetaxel, carboplatin, trastuzumab (Herceptin), and pertuzumab (TCHP) or Adriamycin and cyclophosphamide (AC) times 4 followed by THP. That would be 4 to 6 cycles of a pertuzumab-containing regimen. 

[With the approval], another 11 to 13 doses can be given, which was the NCCN guideline. Many of us thought they were jumping the gun when they initially stated this without clinical data, but this has been proven to be true to some degree. There is a benefit with that since many are already using pertuzumab and this is just adding more.

However, we are not sure if it is necessary. Therefore, this becomes a test of 6 doses of pertuzumab, which has benefits in terms of pathologic complete response (pCR) and DFS versus an adjuvant trial where no one received pertuzumab. It is a 6- versus 17-dose issue. I am not sure how many of us are going to interpret this. The data from APHINITY, which this approval is based on, shows a modest or minimal benefit because the control arm did so well and we already have a 91% 5-year DFS. 

We are not sure if extra pertuzumab is necessary and many of us will struggle with that question. If an oncologist does not think it is necessary, instead of getting upfront adjuvant chemotherapy, many women will have surgery first. If they are lymph node negative with a 2-cm tumor, they will receive adjuvant paclitaxel or trastuzumab for 12 weeks. This will spare them more intensive chemotherapy and patients will still see a 4- or 5-year DFS. Many of us will give neoadjuvant therapy upfront with pertuzumab and decide whether we are going to give the next several doses. 

Neratinib was also approved in this space in 2017. Can you discuss its role?

Mostly everyone will receive trastuzumab, whereas some patients may also receive pertuzumab if they are node-positive after neoadjuvant therapy or after surgery without neoadjuvant therapy. The women who will likely receive this are high-risk upfront. Women with positive lymph nodes who do not have a pCR rate, will receive 1 year of trastuzumab or pertuzumab and then will likely receive 1 year of neratinib.

Neratinib’s major adverse event (AE) is diarrhea. Even with intensive prophylaxis, it is still seen in 10% to 15% of patients as a grade 3 AE. A couple of months of antidiarrheal medications are needed to get the patient through the tachyphylaxis stage. I would not prescribe neratinib for women with node-negative estrogen receptor (ER)-positive or HER2-positive breast cancer. However, for someone who has a 5-cm tumor and it is still at 3- to 4-cm after 1 year of trastuzumab or pertuzumab, I would then give neratinib. This is around 20% to 25% of women.

Will neratinib be combined with other agents for this patient population?

We don’t know. We could see that giving neratinib upfront with trastuzumab is the way to go. People are probably going to give it as [indicated] in the label. I do not believe that people will start giving it earlier.

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