Targeting HER2-positive Breast Cancer

The FDA has approved a new HER2-targeted therapeutic for the treatment of certain patients with early-stage breast cancer.

The U.S. Food and Drug Administration (FDA) recently approved a new molecularly targeted therapeutic called neratinib (Nerlynx) for treating certain patients with HER2-positive breast cancer.

Neratinib is intended for patients with early-stage HER2-positive breast cancer who have completed a year’s treatment with trastuzumab (Herceptin).

In 2017, it is expected that there will be 252,710 new cases of breast cancer diagnosed in the United States, according to National Cancer Institute SEER data. This makes breast cancer the most commonly diagnosed cancer in the United States.

Up to 20 percent of breast cancers have elevated levels of the protein HER2. This type of the disease, which is often referred to as HER2-positive breast cancer, tends to be aggressive. The outcome for patients was typically poor until research led to the development and FDA approval of HER2-targeted therapeutics. Trastuzumab (Herceptin) was the first of these groundbreaking therapeutics to be approved by the FDA, in 1998.

One use for trastuzumab in the treatment of patients with HER2-positive breast cancer is as an adjuvant treatment for those with early-stage disease, meaning that it is given after the patient has completed initial treatment to lower the risk that the cancer will recur. In this setting, trastuzumab is usually given for one year after surgery and chemotherapy.

Even though one year of adjuvant trastuzumab significantly improved outcomes for patients with early-stage HER2-positive breast cancer, more than 20 percent of patients still have disease recurrence. Therefore, researchers set out to test whether extending adjuvant treatment with another HER2-targeted therapeutic could reduce the risk of recurrence for these patients.

Results from the randomized, placebo-controlled phase III ExteNET clinical trial, which led to this week’s approval, showed that extending adjuvant treatment for 12 months with neratinib did indeed reduce the risk of disease recurrence among women with early-stage HER2-positive breast cancer who had already completed a year of adjuvant trastuzumab. The results, which were published in Lancet Oncology, showed that after two years of follow-up, 94.2 percent of women with early-stage HER2-positive breast cancer who received 12 months of neratinib after one year of trastuzumab had no recurrence of invasive disease, compared with 91.9 percent of patients who received placebo rather than neratinib.

Diarrhea was the most common adverse event among those who received neratinib and it led to treatment discontinuation in 17 percent of patients. Thus, the FDA recommends that patients receiving neratinib should be given antidiarrheal prophylaxis for the first 56 days of treatment and as needed thereafter.

The FDA approval was rendered on July 17, 2017.