Positive results have been reported from a phase 3 study of adjuvant treatment with the combination of pertuzumab (Perjeta), trastuzumab (Herceptin), and chemotherapy in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. The combination regimen achieved a statistically significant reduction in the risk of recurrence of invasive disease or death compared with trastuzumab and chemotherapy alone.
Pertuzumab and trastuzumab are marketed in the United States by Genentech, a member of the Roche group. The combination of pertuzumab, trastuzumab, and chemotherapy is currently available under the FDA’s accelerated approval program.
The study results boost Roche’s bid to protect its aging but lucrative oncology franchise from cheaper copies, according to a Reuters report. Trastuzumab, approved in 1998, is losing patent protection, exposing it to competition from a biosimilar version that Mylan and Biocon may introduce in Europe this year.
The APHINITY (Adjuvant Pertuzumab and Herceptin IN Initial TherapY in Breast Cancer) trial was an international, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of pertuzumab plus trastuzumab and chemotherapy compared with that of trastuzumab and chemotherapy as an adjuvant therapy in 4,805 patients with operable HER2-positive early breast cancer. Patients enrolled in the study underwent surgery and were randomly assigned to one of two treatment arms:
In the study, radiotherapy and/or endocrine therapy could be initiated at the end of adjuvant chemotherapy. The study also allowed a range of standard chemotherapy regimens to be used, and both lymph node-positive and lymph node-negative participants were eligible for enrollment. The primary efficacy endpoint was invasive disease-free survival. Secondary endpoints included cardiac and overall safety, overall survival, disease-free survival, and health-related quality of life.
Pertuzumab targets the HER2 receptor, a protein found on the outside of many normal cells and in high quantities on the outside of cancer cells in HER2-positive cancers. Pertuzumab is designed specifically to prevent the HER2 receptor from pairing (or ‘dimerising’) with other HER receptors (i.e., EGFR/HER1, HER3, and HER4) on the surface of cells, a process that is believed to play a role in tumor growth and survival. Binding of pertuzumab to HER2 may also signal the body’s immune system to destroy the cancer cells. The mechanisms of action of pertuzumab and trastuzumab are believed to complement each other, as both bind to the HER2 receptor, but to different places, according to Roche.