No Progression-Free Survival Benefit for First-Line Neratinib/Paclitaxel vs Trastuzumab/Paclitaxel in Metastatic HER2-Positive Breast Cancer
In the phase III NEfERT-T trial reported in JAMA Oncology, Awada et al found no progression-free survival benefit of neratinib/paclitaxel vs trastuzumab (Herceptin)/paclitaxel in previously untreated inoperable recurrent or metastatic HER2-positive breast cancer. A potential benefit of neratinib/paclitaxel was found in reducing risk of central nervous system (CNS) progression.
Study Details
In the open-label trial, 479 women from 188 sites in 34 countries were randomized between August 2009 and December 2014 to neratinib at 240 mg/d (n = 242) or trastuzumab at 4 mg/kg followed by 2 mg/kg weekly (n = 237), each in addition to paclitaxel at 80 mg/m2 on days 1, 8, and 15, every 28 days. Women with asymptomatic CNS metastases were eligible for the study, and randomization was stratified by prior trastuzumab and lapatinib (Tykerb) therapy, hormone-receptor status, and region. The primary outcome was progression-free survival.
Outcomes
Median follow-up was 23.0 months. Median progression-free survival was 12.9 months with neratinib/paclitaxel vs 12.9 months with trastuzumab/paclitaxel (hazard ratio [HR] = 1.02, P =.89). Patients in the neratinib/paclitaxel group had reduced risk of CNS recurrence (relative risk = 0.48, P = .002) and prolonged time to CNS metastases (HR = 0.45, P = .004).
Adverse Events
Primary prophylaxis for diarrhea, a common toxic effect of neratinib, was not mandatory, and grade 3 diarrhea was reported in 30.4% of the neratinib group vs 3.8% of the trastuzumab group. Other common grade 3 or 4 adverse events included neutropenia (12.9% vs 14.5%) and leukopenia (7.9% vs 10.7%).
The investigators concluded, “In first-line ERBB2-positive metastatic breast cancer, neratinib/paclitaxel was not superior to trastuzumab/paclitaxel in terms of progression-free survival. In spite of similar overall efficacy, neratinib/paclitaxel may delay the onset and reduce the frequency of central nervous system progression, a finding that requires a larger study to confirm.”
The study was sponsored by Wyeth, Pfizer, and Puma Biotechnology, Inc.
Ahmad Awada, MD, PhD, of Jules Bordet Institute, is the corresponding author for the JAMA Oncology article.
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