Neratinib plus paclitaxel was not superior to trastuzumab plus paclitaxel with respect to progression-free survival as first-line treatment for patients with ERBB2-positive metastatic breast cancer, a study published in JAMA Oncology has shown.1

Neratinib is an irreversible pan-ERBB tyrosine kinase inhibitor. Researchers sought to compare progression-free survival with neratinib with that of trastuzumab, in combination with paclitaxel, for the first-line treatment of recurrent and/or metastatic ERBB2-positive breast cancer.

For the international, open-label, controlled NEfERT-T trial, researchers enrolled 479 women with previously untreated recurrent and/or metastatic ERBB2-positive breast cancer. Participants were randomly assigned 1:1 to receive neratinib 240 mg orally daily or trastuzumab 4 mg/kg then 2 mg/kg IV weekly, each combined with paclitaxel 80 mg/m2 IV on days 1, 8, and 15 every 28 days. Some patients also received primary prophylaxis for diarrhea.

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Results showed that median progression-free survival was 12.9 months (95% CI, 11.1-14.9) with neratinib plus paclitaxel vs 12.9 months (95% CI, 11.1-14.8) with trastuzumab plus paclitaxel (HR, 1.02; 95% CI, 0.81-1.27; P = .89).

Researchers found that incidence of central nervous system (CNS) recurrences was lower (RR, 0.48; 95% CI, 0.29-0.79; P = .002) and time to CNS metastases was delayed (HR, 0.45; 95% CI, 0.26-0.78; P = .004) with neratinib plus paclitaxel compared with chemoimmunotherapy.

With regard to safety, the most common grade 3 or 4 adverse events were diarrhea (30.4% with neratinib-paclitaxel vs 3.8% with trastuzumab-paclitaxel), neutropenia (12.9% vs 14.5%), and leukopenia (7.9% vs 10.7%).

Although the 2 combinations demonstrated similar overall efficacy, neratinib plus paclitaxel was associated with delayed onset and reduced frequency of CNS progression. A larger study is needed to confirm those findings.


1. Awada A, Colomer R, Inoue K, et al. Neratinib plus paclitaxel vs trastuzumab plus paclitaxel in previously untreated metastatic ERBB2-positive breast cancer: The NEfERT-T randomized clinical trial [published online ahead of print April 14, 2016]. JAMA Oncol. doi:10.1001/jamaoncol.2016.0237.