FDA has approved Genentech’s Perjeta (pertuzumab), in combination with Herceptin (trastuzumab) and chemotherapy (the Perjeta-based regimen), for adjuvant treatment of HER2-positive early breast cancer at high risk of recurrence.
Genentech is a member of the Roche Group.
Patients should receive the adjuvant Perjeta-based regimen for one year (up to 18 cycles).
FDA has also converted the previously granted accelerated approval of the Perjeta-based regimen to full approval for neoadjuvant treatment of HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either greater than two centimeters in diameter or node-positive). People receiving the neoadjuvant Perjeta-based regimen should continue Perjeta and Herceptin after surgery to complete one year of treatment.
The FDA-approved use of the Perjeta-based regimen for adjuvant treatment of HER2-positive EBC at high risk of recurrence is based on results of the phase III APHINITY study. At the time of the primary analysis with a median of 45.4 months follow-up:
In the overall study population, Perjeta, Herceptin and chemotherapy significantly reduced the risk of invasive breast cancer recurrence or death by 18 percent compared to Herceptin and chemotherapy alone (HR=0.82, 95% CI 0.67-1.00, p=0.047).
High-risk patients included patients such as those with lymph node-positive or hormone receptor-negative breast cancer. The subgroup results were as follows:
Lymph node-positive subgroup (HR=0.77, 95% CI 0.62-0.96)
Hormone receptor-negative subgroup (HR=0.76, 95% CI 0.56-1.04)
Hormone receptor-positive subgroup (HR=0.86, 95% CI 0.66-1.13)
Lymph node-negative subgroup (HR=1.13, 95% CI 0.68-1.86)
The most common severe (grade III-IV) side effects with the Perjeta-based regimen are low levels of white blood cells with or without a fever, diarrhea, decrease in certain types of white blood cells, decrease in red blood cells, fatigue, nausea and mouth blisters or sores. The most common side effects are diarrhea, nausea, hair loss, fatigue, nerve damage and vomiting.
The supplemental Biologics License Application for the Perjeta-based regimen for adjuvant treatment of HER2-positive EBC was granted Priority Review, a designation given to medicines the FDA has determined to have the potential to provide significant improvements in the treatment, prevention or diagnosis of a disease.
Perjeta is also approved for use in combination with Herceptin and docetaxel in people who have HER2-positive breast cancer that has spread to different parts of the body and who have not received anti-HER2 therapy or chemotherapy for metastatic breast cancer.
APHINITY (Adjuvant Pertuzumab and Herceptin IN Initial TherapY in Breast Cancer, NCT01358877/ BO25126/ BIG 4-11) is an international, phase III, randomized, double-blind, placebo-controlled, two-arm study evaluating the efficacy and safety of Perjeta plus Herceptin and chemotherapy compared to Herceptin and chemotherapy as adjuvant therapy in 4,805 people with operable HER2-positive EBC.
The primary efficacy endpoint of the APHINITY study is invasive disease-free survival, which in this study is defined as the time a patient lives without return of invasive breast cancer at any site or death from any cause after adjuvant treatment. Secondary endpoints include cardiac and overall safety, overall survival, disease-free survival and health-related quality of life. The study will continue to follow participants for ten years.
