Combination Treatment Reduces Risk of Recurrence in HER2-Positive Early Breast Cancer

Adjuvant treatment with pertuzumab (Perjeta) in combination with trastuzumab (Herceptin) and chemotherapy significantly reduced the risk of breast cancer recurrence or death in patients with early breast cancer.

Pertuzumab is designed to target the HER2 receptor and prevent it from pairing with EGFR/HER1, HER3, and HER4 on the surface of cells, according to a press release. The combination of pertuzumab and trastuzumab are believed to complement each other because both bind to the HER2 receptor, but in different areas.

The randomized, double-blind, placebo-controlled, 2-arm phase 3 APHINITY study examined the safety and efficacy of pertuzumab plus trastuzumab and chemotherapy compared with trastuzumab as adjuvant therapy. Included in the study were 4805 patients with operable HER2-positive early breast cancer.

The participants were randomized to either receive 6 to 8 cycles of chemotherapy with pertuzumab and trastuzumab, followed by pertuzumab and trastuzumab every 3 weeks for 1 year, or 6 to 8 cycles of chemotherapy with placebo and trastuzumab, followed by placebo and trastuzumab every 3 weeks for 1 year.

The primary endpoint is invasive disease-free survival (iDFS), defined as the time a patient lives without invasive breast cancer recurrence at any site or death from any cause after adjuvant treatment. Secondary endpoints were cardiac and overall safety, overall survival, disease-free survival, and health-related quality of life.

The results of the study showed that adjuvant treatment with pertuzumab, trastuzumab, and chemotherapy significantly reduced the risk of breast cancer recurrence or death by 19% in patients with HER2-positive early breast cancer compared with trastuzumab and chemotherapy alone.

At 3 years, 94.1% of patients in the pertuzumab-based regimen did not have recurrence compared with 93.2% treated with trastuzumab and chemotherapy, according to the press release.

Based on available data at the time of primary analysis, the investigators found that at 4 years, an estimate of iDFS showed that 92.3% of patients treated with the pertuzumab-based regimen did not have their breast cancer return compared with 90.6% of patients in the trastuzumab and chemotherapy arm.

The data suggests that further analyses with a longer follow-up will be critical to provide additional information on the treatments.

“The goal of adjuvant treatment is to help each person with cancer have the best chance of a cure, and we come closer to this goal with each advance," Sandra Horning, MD, chief medical officer and head of Global Product Development at Genentech, said in a release. “In the APHINITY study, the Perjeta-based regimen improved upon the high bar set by Herceptin in people with HER2-positive early breast cancer. We look forward to working with global health authorities to bring this treatment option to patients.”

At the time of the primary analysis the reduction in the risk of invasive breast cancer recurrence in the pertuzumab-based regimen group was greatest in patients with lymph node-positive or hormone receptor-negative disease.

Among patients with node-positive disease, 92% treated with the pertuzumab-based regimen did not have recurrence compared with 90.2% treatment with trastuzumab and chemotherapy at 3 years. Furthermore, iDFS rates in the hormone receptor-negative disease subgroup was 92.8% among the pertuzumab-based arm and 91.2% in the trastuzumab and chemotherapy arm.

“APHINITY provides yet another example of the importance of industry-academic collaborations and their value in advancing cancer care for people affected by this challenging disease,” Gunter von Minckwitz, MD, study coordinator and president of the German Breast Group, said in a release. “The median follow-up at the primary analysis was 45.4% months, and these early data are very encouraging. As we continue to follow patients up to 10 years, we hope that future analyses will provide additional insights on the role of a pertuzumab-based regimen in HER2-positive early breast cancer.”

The findings were presented at the American Society of Clinical Oncology annual meeting in Chicago.