FDA OKs First 'Extended' Adjuvant Treatment for HER2 Breast Cancer

Nick Mulcahy

July 17, 2017

The US Food and Drug Administration (FDA) approved neratinib (Nerlynx, Puma Biotechnology) today for the treatment of early-stage, HER2-positive breast cancer.

Neratinib is specifically indicated as an "extended adjuvant therapy," according to an FDA news release, to reduce the risk for recurrence in this setting and, as such, is a first. The new drug is for patients who have already completed standard adjuvant treatment with trastuzumab (Herceptin, Genentech/Roche) and have not progressed but would like additional treatment.

The pivotal phase 3 randomized trial consisted of 2840 patients with early-stage, HER2-positive breast cancer who previously had completed trastuzumab treatment. After 2 years, patients treated with 1 year of neratinib had a disease-free survival rate of 94.2% versus 91.9% of patients on placebo.

"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, from the FDA's Center for Drug Evaluation and Research, in a press statement. "Now, these patients have an option after initial treatment that may help keep the cancer from coming back."

Neratinib is an oral tyrosine kinase inhibitor that works by blocking several enzymes that promote cancer cell growth.

Common side effects of neratinib include diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, liver damage (AST or ALT enzyme increase), nail disorder, dry skin, abdominal distention, weight loss, and urinary tract infection.

Almost 40% of patients in the phase 3 study had grade 3 diarrhea within the first 30 days, according to a data presentation at the 2015 San Antonio Breast Cancer Symposium. However, notably, no prophylactic loperamide was given.

The FDA says that patients should be given loperamide for the first 56 days of treatment with neratinib and as needed thereafter. Additional antidiarrheals, fluids, and electrolytes should also be given as clinically indicated. Patients who experience severe side effects, including diarrhea or liver damage, should discontinue neratinib.

US oncologists anticipate using the new drug, according to a recent Medscape poll of 93 such clinicians. In the survey, 88% indicated that they would use neratinib to treat their HER2-positive breast cancer patients.

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