The 5-year analysis of the phase III ExteNET trial has shown that 1 year of neratinib (Nerlynx) after trastuzumab (Herceptin)-based adjuvant therapy significantly improved invasive disease–free survival vs placebo in HER2-positive breast cancer. These findings were reported in The Lancet Oncology by Martin et al.
In the ongoing double-blind trial, 2,840 patients from sites in 40 countries were randomized between July 2009 and October 2011 to receive neratinib at 240 mg/d (n = 1,420) or placebo (n = 1,420) for 1 year. Patients had completed neoadjuvant and adjuvant chemotherapy plus trastuzumab with no evidence of disease recurrence or metastatic disease at study entry. Randomization was stratified by hormone receptor status, nodal status, and sequential vs concurrent adjuvant trastuzumab regimen.
Primary analysis of the trial showed improved 2-year invasive disease–free survival with neratinib. The current report is a protocol-defined 5-year sensitivity analysis with invasive disease–free survival in the intent-to-treat population as the primary endpoint.
Invasive Disease–Free Survival
After a median follow-up of 5.2 years, the neratinib group had significantly fewer invasive disease–free survival events vs the placebo group (116 vs 163 events, stratified hazard ratio = 0.73, P = .0083), with 5-year invasive disease–free survival rates of 90.2% vs 87.7%.
A safety update showed that, without diarrhea prophylaxis, the most common grade 3 or 4 adverse events in the neratinib vs placebo groups were diarrhea (40% vs 2%), vomiting (3% vs < 1%), and nausea (2% vs < 1%). Serious adverse events occurred in 7% vs 6%. There was no evidence of an increased risk of long-term toxicity or long-term adverse consequences of neratinib-associated diarrhea.
The investigators concluded: “At the 5-year follow-up, 1 year of extended adjuvant therapy with neratinib, administered after chemotherapy and trastuzumab, significantly reduced the proportion of clinically relevant breast cancer relapses—ie, those that might lead to death, such as distant and locoregional relapses outside the preserved breast—without increasing the risk of long-term toxicity. An analysis of overall survival is planned after 248 events.”
The study was funded by Wyeth, Pfizer, and Puma Biotechnology.
Miguel Martin, MD, of Instituto de Investigación Sanitaria Gregorio Marañón, Universidad Complutense, Madrid, is the corresponding author of The Lancet Oncology article.
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