Neratinib after trastuzumab-based adjuvant therapy favourable in HER2-positive breast cancer
The 5-year analysis of the ExteNET trial recently confirmed sustained benefit with neratinib after trastuzumab-based adjuvant therapy in patients with early-stage HER2-positive breast cancer, according to results presented at the European Society for Medical Oncology (ESMO) 2017 Congress held in Madrid, Spain.
In this 5-year analysis of the intention-to-treat (ITT) population of 2,840 patients enrolled in the multicentre, randomized, double-blind, placebo-controlled, phase III ExteNET trial, patients who received neratinib 240 mg daily for 1 year after adjuvant trastuzumab and chemotherapy fared better than those who received placebo (invasive disease free survival [iDFS], 90.2 vs 87.7 percent; hazard ratio [HR], 0.73; p=0.008). [ESMO 2017, abstract 149O]
Analysis of the cohort based on hormone receptor status also showed higher iDFS in the neratinib vs placebo group among patients with hormone receptor-positive disease (91.2 vs 86.8 percent; HR 0.60; p=0.002).
Disease-free survival (DFS) was also higher with neratinib vs placebo in the ductal carcinoma in situ (DCIS) cohort (89.7 vs 86.8 percent; HR 0.71; p=0.004).
Distant DFS (p=0.065) and time to distant recurrence (p=0. 078), however, did not differ significantly between the neratinib and placebo groups.
The overall survival (OS) data are expected to mature in 2019.
“This analysis shows a 2.5 percent absolute benefit in the ITT population and a 4.4 percent absolute benefit in the hormone receptor-positive cohort,” commented investigator Professor Miguel Martin, Head of the Medical Oncology Service at the Hospital General Universitario Gregorio Marañón in Madrid, Spain.
In a separate study, neratinib was associated with a decrease in health-related quality of life scores at 1 month compared with placebo (adjusted mean differences: FACT-B total, -2.9 points; EQ-5D index, -0.02). The authors of the study suggested that this may be attributable to the diarrhoea associated with neratinib treatment. The between-group differences, however, decreased at later time points. [ESMO 2017, abstract 177P]
“The results of the [ExteNET] trial showed continued clinically significant benefit, especially in high-risk hormone receptor-positive disease… Diarrhoea can be reduced significantly with prophylaxis, which is a component of treatment,” said discussant Professor Hope Rugo, Director of the Breast Oncology and Clinical Trials at University of California San Francisco Comprehensive Cancer Center, California, US.
The ExteNET trial had previously shown a significant iDFS benefit with neratinib treatment at 2-year follow-up as compared with placebo among patients with HER2-positive, adjuvant-pretreated breast cancer (93.9 vs 91.6 percent; HR, 0.67; p=0.0091).[Lancet Onco 2016;17:367-377]
Fifteen to 24 percent of early-stage HER2-positive breast cancer patients relapse despite trastuzumab and chemotherapy after a median of 8–11 years, necessitating new adjuvant treatment options.[J Clin Oncol 2014;32:3744-3752]