> Pertuzumab benefits some when given with Herceptin

Pertuzumab benefits some when given with Herceptin


People with higher risk of recurrence gain the most by taking the medicine than people with average or low risk

Pertuzumab (Perjeta) was FDA approved for use in high-risk early-stage breast cancer in December 2017. This article explains the clinical trial research that supported the FDA approval. 

Adding the targeted therapy pertuzumab (Perjeta) to standard anti-HER2 treatment of chemotherapy and trastuzumab (Herceptin) for early-stage, HER2-positive breast cancer resulted in more people living at least 3 years without a recurrence, a phase III study found.

Though the trial’s results are considered positive overall, the difference between the group taking pertuzumab and the group getting standard care was small. Those who saw the most improvement with pertuzumab were people deemed to have a higher risk of recurrence.


HER2-postive breast cancer, cancer that has too much of a protein called human epidermal growth factor receptor 2 (HER2), makes up about one-fifth of all breast cancer diagnoses. These cancers were once harder to treat than other types, but the development of the targeted therapy trastuzumab, which was approved by the FDA in 1998, has led to better outcomes for people with this type of the disease.

Pertuzumab also targets HER2 receptors. It is currently FDA approved for people with metastatic breast cancer and as a pre-surgery, or neoadjuvant, treatment for early-stage breast cancer. Because pertuzumab and trastuzmab target receptors on different parts of the cell, researchers designed the APHINITY trial to see if combining the two treatments could lead to a higher rate of invasive disease-free survival, or more people living longer without breast cancer returning.


The APHINITY trial is a phase III, double-blind trial. A total of 4,805 people were randomly assigned to get either

  • pertuzumab with the standard treatment of chemotherapy and trastuzumab, or
  • placebo with the standard treatment of chemotherapy and trastuzumab

The main interest of the study was invasive disease-free survival, or the time between starting treatment and a recurrence or death. The study also looked at other measures of the medicine’s effectiveness, including overall survival and quality of life.


The trial met its main goal in finding that more people reached 3 years without a recurrence when they received pertuzumab instead of a placebo, but the difference in invasive disease-free survival was small, at less than 1 percent:

  • 94.1 percent of people in the pertuzumab group lived at least 3 years without a recurrence
  • 93.2 percent of people in the placebo group lived at least 3 years without a recurrence

When the researchers looked at certain sub-groups they found that people who had a higher risk of recurrence were more likely to benefit from the addition of pertuzumab. Participants were considered to have higher risk of recurrence if breast cancer was found in one or more lymph nodes, or if it was hormone receptor-negative.  Of the 3,005 people with cancer found in one or more lymph nodes:

  • 92.0 percent of people in the pertuzumab group lived at least 3 years without a recurrence
  • 90.2 percent of people in the placebo group lived at least 3 years without a recurrence

When the researchers looked at people who did not have cancer in the lymph nodes, they found that there were very few cases of recurrence. In these cases they saw no benefit to adding pertuzumab to treatment for this group.

No unexpected side effects were seen with the combination of pertuzumab and standard treatment, but there were higher levels of some side effects that have been associated with these treatments, most notably diarrhea.

What this means for you

Adding pertuzumab to treatment with chemotherapy and trastuzumab showed a benefit that wasn’t caused by chance. But that benefit was small. For the study group as a whole, less than 1 percent of people benefitted from the addition.

When this study was presented at the American Society of Clinical Oncology meeting in June, it was suggested that doctors consider using it for node-positive cancers. If cancer was found in your lymph nodes or the disease is hormone receptor-negative, there is a higher chance cancer may come back. Because of the higher risk, you may feel that any change in those chances to be helpful. In addition, pertuzumab was shown to do better in these groups. People with hormone receptor-negative breast cancer had a 1.6 percent higher chance of reaching 3 years without cancer returning than did the placebo group, and people with cancer in their lymph nodes had a 1.8 percent higher chance.

Any benefit is important to consider, but you may be concerned about the cost, both physically and financially, of adding another medicine to treatment for such a small chance of being helped, even if there were few additional side effects.

Speak with your doctor about the risks of your particular diagnosis and why they do or do not recommend a certain treatment.


von Minckwitz, G; Procter, M; de Azambuja, E; et al. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer. NEJM. Published online before print June 5, 2017. DOI: 10.1056/NEJMoa170364