Phase 3 clinical trial evaluating the safety and efficacy of adding pertuzumab to trastuzumab and docetaxel therapy in patients with HER2+ metastatic breast cancer

This phase 3 clinical trial evaluated the safety and efficacy of adding pertuzumab to trastuzumab and docetaxel for the treatment of patients with HER2+ metastatic breast cancer (mBC).

Some breast cancer cells have on their surface some proteins called human epidermal growth factor receptor 2 (HER2) that help them grow. These are called HER2-positive (HER2+) breast cancers. These types of breast cancer tend to be more aggressive and fast-growing than other breast cancers. Therefore, many patients with HER2+ breast cancers have an advanced stage. This means that the cancer has spread to the lymph nodes or to other tissues and organs (mBC). Also, these types of breast cancer are less likely to respond to therapy. However, treatments that specifically target the HER2 proteins on the surface of the cancer cells are very effective. The standard treatment for women with HER2+ mBC is trastuzumab (Herceptin) alone, or in combination with chemotherapy drug docetaxel (Taxotere). Pertuzumab (Perjeta) is a drug newly approved by the U.S. FDA for the treatment of patients with HER2+ mBC in combination with trastuzumab and docetaxel. It works by binding to the HER2 proteins on the surface of the cancer cells and helps destroy them, killing the cancer cells in the process. 

808 women with HER2+ mBC were included in this study. Patients were randomly assigned to receive either the combination pertuzumab, trastuzumab and docetaxel (pertuzumab group – 402 patients) or placebo (a substance with no medical effect, used as control in testing new drugs), trastuzumab and docetaxel (placebo group – 406 patients) every three weeks. The main parameters evaluated were progression-free survival or PFS (the percentage of patients who have survived for a defined period of time, without progression of their cancer) and overall survival or OS (defined as the percentage of patients who have survived for a certain period of time after treatment), as well as side effects to the treatment.

After approximately 2.5 years of follow up, the average PFS was 12.4 months in the placebo group, compared to 18.7 months in the pertuzumab group. Also, OS was 34% longer in the pertuzumab group than in the placebo group. However, more patients in the pertuzumab group reported side effects compared to the placebo group (36% versus 29%). The most common side effects reported by both groups were diarrhea, hair loss, nausea, risk of infection and tiredness.  

In summary, the addition of pertuzumab to trastuzumab and docetaxel therapy showed a significant survival benefit for patients with HER2+ mBC.

This trial served as grounds for the approval of pertuzumab in combination with trastuzumab and docetaxel for the treatment of patients with HER2+ mBC.

This study was funded by Roche, the manufacturer of Perjeta.