A recent paper published in The New England Journal of Medicine, shows that Pertuzumab, an anti-HER 2 antibody, recognizes a different epitope of HER2 than Trastuzumab and behaves differently. In patients with metastatic breast cancer, the combination of the two antibodies plus docetaxel significantly increased progression-free survival.
Co-author Javier Cortés, Principal Investigator of VHIO´s Breast Cancer and Melanoma Group, describes the CLEOPATRA (CLinical Evaluation Of Pertuzumab And TRAstuzumab) randomized trial, the importance and implications of the findings, as well as signposts future directions:
Monoclonal antibodies have become a critical tool in the management of solid tumors. Regarding breast cancer, the HER2 subtype is characterized by a membrane receptor called HER2, which confers a poor prognosis. Over the last decade trastuzumab, a monoclonal antibody against HER2, has improved the prognosis of this disease not only in the metastatic setting but also in the (neo)adjuvant scenario.
While trastuzumab has indeed shown improved progression-free survival and overall survival in combination with chemotherapy, in the majority of cases the disease will progress and those patients will die. New drugs to improve disease control are therefore critically important.
The CLEOPATRA study explored the combination of pertuzumab - a new anti-HER2 antibody which prevents the dimerization between HER2 and other HER family members, with the standard docetaxel and trastuzumab combination in metastatic breast cancer.
Pertuzumab showed to improve the primary endpoint of the study, progression-free survival (PFS) and may also improve overall survival. The median PFS was more than 18 months, which is not only impressive, but also of immense clinical importance and - more importantly - without significant adverse events.
These findings, recently reported at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium (December 6-10), not only represent an important step forward in the treatment of this advanced breast cancer but also have two immediate consequences:
First, patients will be able to have the disease controlled for longer periods of time, without having to change to more aggressive regimens. Secondly, we have established another standard of care so this can be the new control arm to continue improving the prognosis of this disease. It is highly likely that this new drug will be approved for primary tumors over the next few years.
If the ongoing clinical trials confirm what we expect, pertuzumab might also help to cure HER2 positive primary tumors and will therefore be an important tool over the next 5 years.