Expert Weighs In on Optimal Perjeta Use in HER2-Positive Breast Cancer

Breast cancer specialist Mark Pegram discusses recent breast cancer studies and what's to come for patients with HER2-positive breast cancer.
In 2013, Perjeta (pertuzumab) in combination with Herceptin (trastuzumab) and chemotherapy became the first neoadjuvant regimen formally approved by the Food and Drug Administration (FDA) for the treatment of patients with breast cancer. The accelerated approval, based on the phase 2 NeoSphere trial, offered an exciting treatment option for patients with HER2-positive locally advanced or early-stage disease. Results from the confirmatory phase 3 APHINITY trial are now eagerly awaited.

Perjeta has also shown impressive outcomes in patients with metastatic HER2-positive disease. Adding Perjeta to Herceptin and chemotherapy improved median overall survival (OS) by almost 16 months over Herceptin and docetaxel alone, according to long-term follow-up from the phase 3 CLEOPATRA study.

In an interview, Mark D. Pegram,  associate director of clinical research and director of the Breast Cancer Program at Stanford Cancer Institute, discusses what the available data suggest is the optimal use of Perjeta for the management of HER2-positive breast cancer.

Please discuss completed and ongoing research involving neoadjuvant Perjeta in HER2-positive early breast cancer.

Dr Pegram: I think the most progress that we have seen in HER2-positive early breast cancer in the neoadjuvant setting are the randomized trials involving the addition of pertuzumab to chemotherapy and trastuzumab. What has been observed in the NeoSphere trial is an increase in the fraction of patients who enjoy a pathologic complete response, which, based on several studies correlates with freedom from relapse. That is promising data, although it is not event-driven data. Based on recent FDA guidance, those types of data sets are sufficient for consideration of an accelerated approval designation, pending a larger randomized phase III trial in the adjuvant setting to confirm that the addition of pertuzumab will be impactful above and beyond chemotherapy and trastuzumab.

The APHINITY trial is ongoing and will do just that; it is the confirmatory phase 3 trial. The FDA granted an accelerated approval for pertuzumab in the neoadjuvant setting because proof of efficacy was demonstrated with the pathologic complete response endpoint. , Some additional safety work was done with a smaller phase 2 randomized trial of different chemotherapy combinations with pertuzumab and trastuzumab, which showed no cardiac safety concerns. Because of that commitment, it went to a large randomized trial. That has really been a breakthrough. It is really practice changing, but we do need to wait for the follow-up phase 3 trial to really know for sure.

If that is a positive study, then I think pertuzumab in the early setting will have traction. If the APHINITY trial is negative, then I think the FDA will probably withdraw their accelerated approval designation for pertuzumab. Everyone is very anxious and excited to see the results of the phase 3 study when it becomes available. The good news is that the trial has already finished accruing and it is in follow-up stages, so we should expect the results in the next couples of years.

What are the challenges associated with using neoadjuvant Perjeta to treat patients with HER2-positive breast cancer?

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