A 5-year sensitivity analysis of a recent trial showed improved efficacy outcomes and toxicity profiles for patients receiving a new adjuvant therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancer, published in The Lancet Oncology (online November 13, 2017; doi:10.1016/s1470-2045(17)30717-9).
A previous trial—ExteNET—indicated that 12 months of therapy with neratinib significantly improves 2-year invasive disease-free survival after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer. However, a long-term analysis of such patients has yet to be conducted.
Miguel Martin, MD, Instituto de Investigación Sanitaria Gregorio Marañón (Madrid, Spain), and colleagues conducted a long-term analysis of ExteNET, which included 2840 patients with early HER2-positive breast cancer from 40 countries who received either neratinib (n = 1420) or placebo (n = 1420) with adjuvant chemotherapy plus trastuzumab. Patients were given treatment continuously for 12 months, unless disease recurrence or new breast cancer, intolerable adverse events, or consent to withdrawal occurred.
After a median follow-up of 5.2 years, researchers reported that patients in the neratinib cohort had significantly fewer invasive disease-free survival events than those in the placebo group (116 vs 163, respectively; stratified HR, 0.73; 95% CI, 0.57-0.92; P = .0083). The 5-year invasive disease-free survival was 90.2% in the neratinib cohort compared with 87.7% in the placebo cohort.
Among the most common grade 3-4 adverse events in the neratinib cohort were diarrhea, vomiting, and nausea. Treatment-emergent serious adverse events occurred in 7% (n = 103) of patients in the neratinib cohort and 6% (n = 85) of patients in the placebo cohort. However, no evidence of increased risk of long-term toxicity of neratinib-associated diarrhea were identified with neratinib compared with placebo.
Results of the 5-year follow-up showed that 12 months of extended adjuvant therapy with neratinib administered after chemotherapy and trastuzumab significantly reduced the proportion of clinically relevant HER2-positive breast cancer relapses without increasing the risk of long-term toxicity, authors of the study concluded. “An analysis of overall survival is planned after 248 events,” they noted.—Zachary Bessette