Affiliation:
1. From the Dana-Farber Cancer Institute, Boston, MA; Oncology Center AZ St Augustinus, Antwerp; UZ Gasthuisberg, Leuven; and Institut Jules Bordet, Brussels, Belgium; Cancer Hospital, Chinese Academy of Medical Sciences; Chinese People's Liberation Army General Hospital; and The Hospital Affiliated Academy of Military Medical Science, Beijing, China; Cancer Institute of New Jersey, New Brunswick, NJ; Deenanath Mangeshkar Hospital, Pune; and Tata Memorial Hospital, Mumbai, India; Dartmouth-Hitchcock Medical...
Abstract
Purpose Neratinib is an oral, irreversible pan-ErbB receptor tyrosine kinase inhibitor. The efficacy and safety of neratinib were evaluated in two cohorts of patients with advanced ErbB2-positive breast cancer—those with and those without prior trastuzumab treatment—in an open-label, multicenter, phase II trial. Patients and Methods Patients in the two cohorts (prior trastuzumab, n = 66; no prior trastuzumab, n = 70) received oral neratinib 240 mg once daily. The primary end point was the 16-week progression-free survival (PFS) rate for the evaluable population (prior trastuzumab, n = 63; no prior trastuzumab, n = 64), as assessed by independent review. Results The 16-week PFS rates were 59% for patients with prior trastuzumab treatment and 78% for patients with no prior trastuzumab treatment. Median PFS was 22.3 and 39.6 weeks, respectively. Objective response rates were 24% among patients with prior trastuzumab treatment and 56% in the trastuzumab-naïve cohort. The most common adverse events were diarrhea, nausea, vomiting, and fatigue. Diarrhea was the most frequent grades 3 to 4 adverse event, occurring in 30% of patients with prior trastuzumab treatment and in 13% of patients with no prior trastuzumab treatment, which prompted dose reductions in 29% and 4% of patients, respectively, but treatment discontinuation in only one patient. No neratinib-related, grades 3 or 4 cardiotoxicity was reported. Conclusion Oral neratinib showed substantial clinical activity and was reasonably well tolerated among both heavily pretreated and trastuzumab-naïve patients who had advanced, ErbB2-positive breast cancer. Diarrhea was the most common adverse effect but was manageable with antidiarrheal agents and dose modification.
Publisher
American Society of Clinical Oncology (ASCO)
Cited by
441 articles.
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