A Phase III Trial of Pertuzumab Retreatment in Previously Pertuzumab Treated Her2-Positive Advanced Breast Cancer

The American Society of Clinical Oncology (ASCO) Clinical Practice Guidelines recommend the use of pertuzumab, trastuzumab and taxane as first-line treatment for patients with MBC. As a second-line treatment, trastuzumab emtansine (T-DM1) is also recommended. After a pertuzumab-containing regimen and T-DM1, other HER2-targeted therapeutic regimens, including lapatinib-containing regimens and trastuzumab plus chemotherapy, are recommended as third-line treatments and beyond. However, continual pertuzumab use for progression after a pertuzumab-containing regimen and retreatment with pertuzumab are unclear based on evidence. The efficacy and the safety of two distinct modalities of a trastuzumab plus pertuzumab-containing regimen after pertuzumab use should be assessed in MBC: continual treatment and retreatment. However, it is clinically difficult to examine the efficacy of continual treatment with a trastuzumab plus pertuzumab-containing regimen because of several circumstances including the results of the MARIANNE study. In addition, it is also important to evaluate the usefulness of retreatment with a pertuzumab-containing regimen. Continual pertuzumab treatment for progression after pertuzumab treatment is not same as pertuzumab retreatment. HER2-HER3-signaling suppressed by pertuzumab-containing regimens could potentially be restored by anti-HER2 therapy without pertuzumab. Pertuzumab retreatment could potentially re-suppress HER2-HER3-signaling. Therefore, Pertuzumab retreatment can be more effective than trastuzumab-containing treatment without pertuzumab.