Drug Reduces Recurrence Risk in Subset of Women with Breast Cancer

Head shot of doctor with glasses, white shirt, and blue tie in his lab.

MSK Physician-in-Chief José Baselga has been a leader in the development and testing of drugs targeting HER2-positive breast cancer.

Update: On December 20, 2017 the FDA approved pertuzumab (Perjeta®) in combination with Herceptin® (trastuzumab) and chemotherapy for adjuvant (after surgery) treatment of HER-2 positive, early-stage breast cancer at high risk of recurrence.

Original post: An important advance in breast cancer treatment has been the emergence of a class of drugs that target the HER2 protein. This receptor on the surface of cells receives growth signals to fuel a tumor. About 20% of breast cancers are considered HER2 positive. The anti-HER2 drug trastuzumab combined with chemotherapy is standard therapy for HER2-positive breast cancer.

Now results from a large phase III clinical trial show that adding a second anti-HER2 drug, pertuzumab, to this combination can reduce the risk of recurrence of invasive disease and death in women with early-stage HER2-positive breast cancer. This finding offers a vital new treatment option for a significant number of women with the disease.

The data are reported at the annual meeting of the American Society of Clinical Oncology and simultaneously published in the New England Journal of Medicine.

“This could become a new standard for treating early breast cancer in many HER2-positive patients,” says José Baselga, Memorial Sloan Kettering’s Physician-in-Chief and a co-corresponding author of the study.

Filling a Treatment Gap

Pertuzumab was initially approved in 2012 for use in women with metastatic HER2-positive breast cancer. That approval was expanded in 2013 to include use in shrinking tumors before surgery. This new study offers hope of filling a gap in treating many women with breast cancer at an early stage, when the growth and spread of the disease can be prevented.

“The only place we can actually cure HER2-positive breast cancer is in the early stage,” Dr. Baselga explains. “These positive results give us a new opportunity to have an impact and improve outcomes.”

In the trial, more than 4,800 participants with HER2-positive breast cancer were randomly assigned to receive chemotherapy plus one year of trastuzumab with either pertuzumab or a placebo. Overall, the group receiving pertuzumab had a three-year invasive-disease-free survival (IDFS) of 94.1%, while those who received a placebo had an IDFS of 93.2%. (This means that 94.1% of participants receiving pertuzumab were estimated to survive for three years without the return of invasive disease.) The side effects from pertuzumab were minimal.

The benefit of pertuzumab was even more pronounced in women who were at a higher risk of relapse. Risk factors included whether the cancer was in the lymph nodes and if the cancer was estrogen receptor negative. This suggests that pertuzumab might be given — at least at first — specifically to HER2-positive women with high-risk disease.

Rapid Progress

Dr. Baselga points out that even participants who received the placebo did well — better than the clinicians predicted at the start of the trial. “This leads you to ask, Is this new drug going to be necessary for everybody? And the answer is probably not,” he says.

A next step might be to test how to improve quality of life with this drug combination. “These results might allow us to begin de-escalating the therapies that can be really tough on patients,” he says. “Chemotherapy can cause serious side effects both during treatment and for a long time afterward.”

Dr. Baselga highlights the impressive progress made in a short time for the care of those with HER2-positive disease — a series of advances in which he has played a leadership role since 2005.

“If you look at the treatment options before trastuzumab compared with the results we’re now seeing with trastuzumab and pertuzumab, the difference is huge,” he says. “In 12 years we have changed in full the natural history of this disease.”