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Neratinib prolongs invasive DFS in HER-2–positive early-stage breast cancer
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CHICAGO — Women with HER-2–positive early-stage breast cancer who received 12 months of neratinib after adjuvant chemotherapy and trastuzumab experienced significant improvements in invasive DFS, according to findings presented at the ASCO Annual Meeting.
Arlene Chan, MD, of the Breast Cancer Research Centre of the Western Australia and Curtin University in Perth, Australia, presented findings for women with stage 1 to 3c early HER-2–positive breast cancer who had received trastuzumab (Herceptin, Genentech) 1 to 2 years prior to the current analysis. Eligible participants received once-daily oral neratinib (PB272, Puma Biotechnology) in 240-mg doses or placebo for 12 months. Researchers stratified patients by ER/PR status, nodal status and trastuzumab schedule.
Two-year invasive DFS served as the primary outcome measure. Secondary endpoints included DFS plus ductal carcinoma in situ (DCIS), distant DFS, central nervous system incidence and patient-reported outcomes.
The analysis included 1,420 patients in each study arm. Median time since trastuzumab treatment was 4.4 months in the study drug arm and 4.7 months in the placebo arm. Other baseline characteristics were well balanced between the two groups.
Mean relative dose intensity was 88% in patients assigned neratinib vs. 98% in patients assigned placebo.
Patients who received study drug demonstrated an improved 2-year invasive DFS rate compared with patients assigned placebo (93.9% vs. 91.6%; HR = 0.67; 95% CI, 0.50-0.91). This translated into an absolute benefit of 2.3%, according to Chan.
“We saw a significant improvement in invasive DFS at 2 years,” she said.
Chan added that the benefit was seen across all subsets and age groups and was not dependent on nodal status or trastuzumab experience.
Neratinib conferred a lower rate of CNS recurrence.
DFS plus DCIS rates also favored neratinib (93.9% vs. 91.0%; HR = 0.63; 95% CI, 0.46-0.84). Similarly, 2-year distant DFS rates were 95.1% for neratinib and 93.7% for placebo (HR = 0.75; 95% CI, 0.53-1.05).
“There was a consistent improvement associated with neratinib treatment,” Chan said.
Neratinib demonstrated benefit in a pre-planned intention-to-treat analysis of invasive DFS in ER/PR-positive patients (HR = 0.51; 0.33–0.77) and in a centrally confirmed HER-2–positive cohort (HR = 0.52; 0.34–0.79).
Diarrhea was the most frequently reported adverse event associated with neratinib (grade 3 or grade 4, 40%).
“Cardiac toxicity was infrequent and generally similar between the two arms,” Chan said.
She concluded that this is the first study to demonstrate a significant invasive DFS benefit of neratinib at 2 years.
“A possible greater benefit in HR-positive disease requires further evaluation in other studies,” she said. – by Rob Volansky
For more information:
Chan AB, et al. Abstract 508. Presented at: ASCO Annual Meeting; May 29-June 2, 2015; Chicago.
Disclosure: Chan reports a consultant/advisory role with Pfizer and a speakers bureau role with and travel expenses from Pierre Fabre.