TY - JOUR
T1 - U.S. Food and drug administration approval
T2 - Neratinib for the extended adjuvant treatment of early-stage HER2-positive breast cancer
AU - Singh, Harpreet
AU - Walker, Amanda J.
AU - Amiri-Kordestani, Laleh
AU - Cheng, Joyce
AU - Tang, Shenghui
AU - Balcazar, Pamela
AU - Barnett-Ringgold, Kimberly
AU - Palmby, Todd R.
AU - Cao, Xianhua
AU - Zheng, Nan
AU - Liu, Qi
AU - Yu, Jingyu
AU - Pierce, William F.
AU - Daniels, Selena R.
AU - Sridhara, Rajeshwari
AU - Ibrahim, Amna
AU - Kluetz, Paul G.
AU - Blumenthal, Gideon M.
AU - Beaver, Julia A.
AU - Pazdur, Richard
N1 - Publisher Copyright:
© 2018 American Association for Cancer Research.
PY - 2018/8/1
Y1 - 2018/8/1
N2 - On July 17, 2017, the FDA approved neratinib (NERLYNX; Puma Biotechnology, Inc.) for the extended adjuvant treatment of adult patients with early-stage HER2-overexpressed/ amplified breast cancer, to follow adjuvant trastuzumab-based therapy. Approval was based on data from ExteNET, a randomized, double-blind, placebo-controlled multicenter trial. Women with early-stage HER2-positive breast cancer and within 2 years of completing adjuvant trastuzumab were randomized to neratinib (n = 1,420) or placebo (n = 1,420) for 1 year. The primary endpoint was invasive disease-free survival (iDFS), defined as the time between randomization date to first occurrence of invasive recurrence (local/regional, ipsilateral, or contralateral breast cancer), distant recurrence, or death from any cause, with 2 years and 28 days of follow-up. The trial showed a statistically significant treatment effect favoring neratinib with a stratifiedHRof 0.66 [95% confidence interval (CI), 0.49-0.90, P = 0.008]. The estimated iDFS rate at 2 years was 94.2% (95% CI, 92.6%-95.4%) in patients treated with neratinib versus 91.9%(95%CI, 90.2%-93.2%) in those receiving placebo. Diarrhea was the most common adverse event (AE), with a 40% incidence of grade 3 or 4 diarrhea, and represents the most common AE leading to treatment discontinuation. Other frequent AEs (>10% incidence) were nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, and muscle spasms. Other than diarrhea, neratinib is associated with a low incidence of severe AEs; toxicities are generally reversible and manageable with dose interruptions, dose reductions, and/or standard medical care. This article summarizes FDA decision-making and data supporting the neratinib approval.
AB - On July 17, 2017, the FDA approved neratinib (NERLYNX; Puma Biotechnology, Inc.) for the extended adjuvant treatment of adult patients with early-stage HER2-overexpressed/ amplified breast cancer, to follow adjuvant trastuzumab-based therapy. Approval was based on data from ExteNET, a randomized, double-blind, placebo-controlled multicenter trial. Women with early-stage HER2-positive breast cancer and within 2 years of completing adjuvant trastuzumab were randomized to neratinib (n = 1,420) or placebo (n = 1,420) for 1 year. The primary endpoint was invasive disease-free survival (iDFS), defined as the time between randomization date to first occurrence of invasive recurrence (local/regional, ipsilateral, or contralateral breast cancer), distant recurrence, or death from any cause, with 2 years and 28 days of follow-up. The trial showed a statistically significant treatment effect favoring neratinib with a stratifiedHRof 0.66 [95% confidence interval (CI), 0.49-0.90, P = 0.008]. The estimated iDFS rate at 2 years was 94.2% (95% CI, 92.6%-95.4%) in patients treated with neratinib versus 91.9%(95%CI, 90.2%-93.2%) in those receiving placebo. Diarrhea was the most common adverse event (AE), with a 40% incidence of grade 3 or 4 diarrhea, and represents the most common AE leading to treatment discontinuation. Other frequent AEs (>10% incidence) were nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, and muscle spasms. Other than diarrhea, neratinib is associated with a low incidence of severe AEs; toxicities are generally reversible and manageable with dose interruptions, dose reductions, and/or standard medical care. This article summarizes FDA decision-making and data supporting the neratinib approval.
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U2 - 10.1158/1078-0432.CCR-17-3628
DO - 10.1158/1078-0432.CCR-17-3628
M3 - Article
C2 - 29523624
AN - SCOPUS:85051143379
SN - 1078-0432
VL - 24
SP - 3486
EP - 3491
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 15
ER -