Neratinib Approved as Extended Adjuvant Breast Cancer Treatment, Carries Diarrhea Risk

The FDA has approved neratinib (Nerlynx) for the extended adjuvant treatment of some forms of breast cancer, but recommends precautions against the common side effect of diarrhea.

As an extended adjuvant treatment, neratinib is intended to be taken after initial treatment to reduce the odds of the cancer returning. Specifically, it is indicated for patients whose early-stage, HER2-positive breast cancer has previously been treated with a trastuzumab-based therapy regimen, according to a press release from the FDA announcing the approval.

A randomized trial of nearly 3000 patients found that 94.2% of those who received neratinib did not experience cancer recurrence or death after 2 years, compared with 91.9% of patients taking a placebo. This ability to keep cancer recurrences at bay is especially important for the 15% of breast cancer patients whose tumors are HER2-positive, FDA officials explained.

“HER2-positive breast cancers are aggressive tumors and can spread to other parts of the body, making adjuvant therapy an important part of the treatment plan,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, in the press statement. “Now, these patients have an option after initial treatment that may help keep the cancer from coming back.”

The approval was accompanied by warnings of the drug’s potential side effects, most notably diarrhea. More than just an unpleasant symptom, the diarrhea associated with neratinib can be severe and cause dehydration. As such, the FDA stated that patients should take loperamide, an anti-diarrheal medication sold over the counter as Imodium, for the first 56 days of treatment and as necessary thereafter. Rates of diarrhea experienced in study populations were not specified in the approval announcement, but a prior report by Advera Health found that 90% of neratinib patients in 11 clinical trials experienced diarrhea, and 19% experienced serious cases, according to a September 2016 FiercePharma article.

At the time, Puma Biotechnology, which manufactures neratinib, sought to downplay these findings. Chief executive Alan Auerbach pointed out to FiercePharma that rates of diarrhea appeared high because few of the studies used loperamide to prevent it. “When you use the Imodium, the rates come down dramatically and it completely changes the safety and tolerability profile of the drug,” he said.

Puma’s press statement in response to the FDA’s approval of neratinib mentions diarrhea as a potentially severe side effect and provides recommendations to mitigate the risk, including taking loperamide. However, the statement mainly focuses on the approval’s implications for women with breast cancer and the improved peace of mind that neratinib could provide after treatment.

“Despite advances in the treatment of early stage HER2-positive breast cancer, there remains a need for further therapeutic improvements in order to attempt to further reduce the risk of disease recurrence,” said Auerbach in the press release. “We are pleased to be able to bring this new medicine to patients with breast cancer.”

Neratinib, which is a tyrosine kinase inhibitor that blocks enzymes that promote cell growth, is currently being reviewed by the European Medicines Agency for sale in Europe. Neither Puma nor the FDA specified a date for when neratinib would enter the US market.