Frontline Pertuzumab for Metastatic Breast Cancer

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The combination of docetaxel (Taxotere), trastuzumab (Herceptin), and pertuzumab (Perjeta) was approved by the FDA to treat patients with HER2-positive metastatic breast cancer based on results from the phase III CLEOPATRA trial. This study provided ample category 1 evidence to support this regimen as the preferred first-line standard of care for patients in this space, moderator Adam M. Brufsky, MD, PhD, states.

At this point in time, the pertuzumab combination is the first-line standard of care. However, Mark D. Pegram, MD, suggests this could change, once results from the phase III MARIANNE trial are made available. This study is exploring T-DM1 plus pertuzumab or placebo versus trastuzumab plus a taxane for patients with untreated metastatic breast cancer.

The most striking item in the CLEOPATRA study was the lack of additional toxicities, Pegram states. Overall the treatment regimen is well tolerated and effective. Adding to this, Kimberly L. Blackwell, MD, suggests that an analysis of the survival curves suggests the majority of the benefits are coming from the two antibodies. As a result, optimal outcomes are still achieved if the chemotherapy is stopped after 6 cycles.

Paclitaxel can be substituted for docetaxel in the combination. In this situation, Hope S. Rugo, MD, recommends dosing paclitaxel continuously for 4 to 6 weeks until a response is achieved. At this point, paclitaxel can be switched to a 2 week on with 1 week off schedule to synchronize with the pertuzumab schedule.

A subset analysis of the CLEOPATRA examined patients that had received prior adjuvant trastuzumab, Pegram notes. Overall, outcomes were similar in these patients to the intent-to-treat population, suggesting that patients who’ve received adjuvant trastuzumab may still benefit from pertuzumab-based first-line treatment.