FDA approves pertuzumab for some early-stage HER2-positive breast cancers

The FDA has approved the use of pertuzumab (Perjeta) given with trastuzumab (Herceptin) and chemotherapy for people with early-stage, HER2-positive breast cancer who have a higher risk of recurrence.

The results were based on the APHINITY trial that showed a slight benefit overall but somewhat stronger results for people who had cancers that were hormone receptor-negative or had cancer found in their lymph nodes.

Background

The APHINITY trial was a phase III, double-blind study designed to see if people with early-stage, HER2-positive breast cancer would benefit from adding pertuzumab to the current standard treatment of chemotherapy and a year of trastuzumab. There were 4,804 people included in the trial randomized to one of two treatment arms:

• 2,400 got chemotherapy with 1 year of trastuzumab and pertuzumab.
• 2,404 got chemotherapy with 1 year of trastuzumab and a placebo.

Maker Genentech first announced in March that the APHINITY trial had met its primary endpoint, showing that there was a lower risk of a recurrence of invasive (stage I or higher) breast cancer or death when taking pertuzumab. But the data were not shared until the American Society of Clinical Oncology meeting in June. The study findings showed a benefit for all study participants that was statistically significant — meaning it was likely not due to chance — but also small. In 3 years of follow up, the study found

• 7.1 percent of people taking pertuzumab had a recurrence or died
• 8.7 percent of people taking the placebo had a recurrence or died

Pertuzumab costs more than what people are already paying for HER2-positive treatment, and the improvement in risk of recurrence or death was less than two percentage points. Doctors at ASCO questioned if they could justify recommending adding nearly $100,000 for treatment that would help such a small percentage of people.

But when researchers looked only at people who had a high risk of recurrence, the data showed a larger improvement from adding pertuzumab.

Looking just at people with hormone receptor-negative breast cancer, which is more likely to recur than other types of breast cancer

• 8.2 percent of those taking pertuzumab had a recurrence or died
• 10.6 percent of those taking the placebo had a recurrence or died

The difference was even larger for those who had breast cancer found in the lymph nodes, sometimes referred to as node-positive disease:

• 9.2 percent of those taking pertuzumab had a recurrence or died.
• 12.1 percent of those taking the placebo had a recurrence or died.

The most common side effects for the pertuzumab group were diarrhea, low white blood cell counts, tiredness and nausea.

The FDA also granted regular approval  for pertuzumab (in combination with trastuzumab and chemotherapy) in neoadjuvant treatment for certain HER2-positive breast cancers. The neoadjuvant use of pertuzumab had been given accelerated approval in 2013, and these further results in early-stage breast cancer completed the required follow up for regular approval. These breast cancers were either inflammatory, locally advanced, had a tumor of more than 2 centimeters, or were node-positive.

What this means for you

Medicines like trastuzumab have greatly lowered the risk of recurrence for early-stage, HER2-positive breast cancers. But certain other features, such as cancer found in the lymph nodes or being HER2-positive and hormone receptor-negative disease, still face a somewhat higher risk. And until now, people with these higher-risk features got the same treatment as people with average risk.

Pertuzumab provides a treatment option to add to standard treatment for people with HER2-positive disease and who are at higher risk for recurrence. The addition of pertuzumab further lowers the risk of a recurrence, with relatively few side effects, but a high financial cost. Speak to your doctor about the risk of recurrence for your diagnosis, financial impacts, and which treatment would be right for you.