Pertuzumab in HER2-positive breast cancer.

BACKGROUND: Lack of response in some patients and relapse during the course of therapy in the treatment of HER2-positive early breast cancer and metastatic breast cancer continue to challenge researchers and clinicians towards a better understanding of the fundamental mechanisms of trastuzumab action and new therapies for HER2. The aim of this review is to discuss current and future treatment options with pertuzumab in the light of new insights into HER2-positive breast cancer.

SCOPE: Pertuzumab showed positive results in clinical studies and agents in routine clinical usage are updated. The PubMed database, ASCO and San Antonio Breast Cancer Symposium Meeting abstracts were searched up to June 2012 by using the terms 'pertuzumab' and 'anti-HER2 treatment'; papers which were considered relevant for the aim of this review were selected by the authors.

FINDINGS: The presented trials of phase II and phase III randomized trials of CLEOPATRA, NEOSPHERE and TRYPHAENA have showed pertuzumab action to be complementary to trastuzumab without increasing adverse events. Adding pertuzumab to trastuzumab in the first line of HER2-positive metastatic breast cancer and in the neoadjuvant treatment of locally advanced HER2-positive breast cancer is usually well tolerated. The evaluation of health-related quality of life showed that combining pertuzumab with docetaxel and trastuzumab compared to placebo have no detrimental effect with adding pertuzumab.

CONCLUSION: Pertuzumab is the first HER dimerization inhibitor with a mechanism of action complementary to trastuzumab. Studies with anti-HER2 combination treatments indicate that the use of more than one HER2-targeted therapy was superior to one of these agents alone. Pertuzumab has produced impressive anti-tumor activity in combination with trastuzumab. There are ongoing studies with pertuzumab with an increasing tendency towards moving the study of these agents to earlier stages of the disease, namely in the adjuvant and neoadjuvant setting.