Neratinib Plus Capecitabine Approved by FDA in HER2-Positive Metastatic Breast Cancer
Posted: Thursday, March 5, 2020
On February 25, the U.S. Food and Drug Administration (FDA) approved a supplemental new drug application for neratinib in combination with capecitabine for the treatment of adult patients with advanced or metastatic HER2-positive breast cancer who have received two or more prior anti–HER2-based regiments in the metastatic setting.
The application approval was based on data from the phase II NALA study. The clinical trial enrolled 621 patients from North America, Europe, Israel, Asia-Pacific, and South America with metastatic HER2-positive breast cancer who had received two or more prior anti–HER2-based regiments in a metastatic setting. Patients were randomly assigned to receive either a 240-mg oral dose of neratinib once per day on days 1 to 21 in combination with capecitabine at 750 mg/m2 given orally twice daily on days 1 to 14 for each 21-day cycle or a 1,250-mg oral dose of lapatinib once daily on days 1 to 21 in combination with capecitabine at 1,000 mg/m2 given orally twice daily on days 1 to 14 for each 21-day cycle.
The study met its primary outcome goals, as progression-free survival was longer in patients treated with neratinib/capecitabine compared with lapatinib/capecitabine (P =.0059). Higher progression-free survival was seen at 12 and 24 months in the neratinib/capecitabine group than in the lapatinib/capecitabine group (29% vs. 15%, 12% vs. 3%, respectively). Median overall survival, objective response rate, and duration of response were longer with the neratinib combination than with the lapatinib combination (21 vs. 18.7 months, 32.8% vs. 26.7%, 8.5 months vs. 5.6 months, respectively).
The most common adverse reactions of any grade (> 5%) to neratinib combination treatment included diarrhea, nausea, vomiting, decreased appetite, constipation, fatigue/asthenia, weight loss, dizziness, back pain, arthralgia, urinary tract infection, upper respiratory tract infection, abdominal distention, renal impairment, and muscle spasms. Frequently reported grade 3 or 4 adverse reactions included diarrhea, nausea, vomiting, fatigue, and appetite loss.
