Paclitaxel With Pertuzumab Plus Trastuzumab in MBC

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The FDA approved pertuzumab in June 2012 to be used in combination with trastuzumab and docetaxel for untreated patients with HER2-positive metastatic breast cancer (MBC). This approval was based on findings from the phase III CLEOPATRA trial. However, following its approval, there was a push led by physicians at Memorial Sloan-Kettering Cancer Center (MSKCC) to allow the regimen to include paclitaxel instead of docetaxel, moderator Adam M. Brufsky, MD, PhD, states. 

At MSKCC, paclitaxel as a monotherapy and in combinations is preferred to docetaxel for the treatment of patients with MBC, suggests Andrew D. Seidman, MD. As a result, the institution undertook a phase II trial examining the safety and efficacy of paclitaxel, pertuzumab, and trastuzumab, which found similar efficacy to the combination with docetaxel.

These efforts culminated in compendia approval and an endorsement from the NCCN guidelines for the combination of weekly paclitaxel with trastuzumab and pertuzumab. However, for patients who receive adjuvant paclitaxel and relapse after a year to a year-and-a-half, docetaxel remains the preferred treatment, Seidman adds.

While the utilization of this regimen is commonly agreed upon in the frontline treatment of HER2-positive patients, determining the optimal second- and third-lines of therapy remains complex. To address this concern, institutions and organizations are developing a set of guidelines specifically for HR and HER2-positive MBC.

In closing, Seidman mentions two trials that helped establish combination strategies for patients with HR- and HER2-positive MBC. The first trial was the TAnDEM trial, which showed that trastuzumab plus anastrozole was superior to anastrozole alone for postmenopausal women. A second trial, Seidman notes, demonstrated that combining letrozole and lapatinib significantly improves progression-free survival for patients with MBC, compared to letrozole alone.