0000000000214559
AUTHOR
Ingrid A. Mayer
Balixafortide (a CXCR4 antagonist) + eribulin in HER2-negative metastatic breast cancer (MBC): Survival outcomes of the phase I trial.
2606 Background: Balixafortide (B) is a potent antagonist of the chemokine receptor CXCR4. Preclinical evidence suggests that disrupting CXCR4 dependent pathways prevents development of breast cancer metastases, enhances the cytotoxic effect of chemotherapy and immunotherapy, and counteracts tumor cell evasion of the immune system. Encouraging safety and efficacy data were published recently from the ongoing Phase 1 trial investigating B + eribulin (E) in patients with HER2 negative MBC (Pernas S. et al. Lancet Oncol. 2018; 19: 812−24). The objective response rate, median progression free survival and median overall survival (OS) for the expanded cohort (EC) and the overall efficacy popula…
Abstract PD3-06: Neratinib + fulvestrant for HER2-mutant, HR-positive, metastatic breast cancer: Updated results from the phase 2 SUMMIT trial
Abstract Background: HER2 mutations define a rare subset of metastatic breast cancer (MBC) with a unique mechanism of oncogenic addiction to HER2 signaling. Neratinib, an irreversible pan-HER tyrosine kinase inhibitor, has demonstrated single-agent clinical activity in HER2-mutant MBC. In HER2-mutant, HR+ MBC, neratinib + fulvestrant (N+F) appears synergistic vs single-agent neratinib, possibly due to more complete inhibition of bi-directional signaling between HER2 and estrogen receptors. Here we describe interim efficacy results of the expanded HER2-mutant, HR+ MBC cohort treated with N+F from SUMMIT (NCT01953926). Methods: HR+ MBC patients (pts) with HER2 mutations documented by local te…
Abstract PD1-05: Latest findings from the breast cancer cohort in SUMMIT - a phase 2 ‘basket’ trial of neratinib + trastuzumab + fulvestrant for HER2-mutant, hormone receptor-positive, metastatic breast cancer
Abstract Background: HER2 mutations are oncogenic in hormone receptor positive (HR+) metastatic breast cancer (MBC), and may confer resistance to prior endocrine therapy but retain sensitivity to neratinib. Neratinib is an oral, irreversible, pan-HER tyrosine kinase inhibitor with clinical activity either as a single agent or in combination with fulvestrant in HER2-mutated, HER2-non-amplified MBC. Genomic analyses suggest that acquired resistance to neratinib can occur via additional HER2 alterations, which may alter HER2-pathway signaling. We investigated whether dual HER2-targeted therapy could improve clinical benefit in a cohort of patients with HER2-mutant, HR+ MBC treated with neratin…
Balixafortide (a CXCR4 antagonist) plus eribulin in HER2 negative metastatic breast cancer: Dose-response analysis of efficacy from phase I single-arm trial.
e15209 Background: Balixafortide (B) is a potent, selective antagonist of the chemokine receptor CXCR4. High CXCR4 levels correlate with aggressive metastatic phenotypes and poor prognosis in metastatic breast cancer (MBC). Efficacy and safety data were published recently from the Phase 1 trial investigating B + eribulin (E) in patients with HER2 negative MBC1. We report the final efficacy analyses from this trial, including assessment of dose-response. Methods: In this single-arm, dose escalation trial, patients (pts) received E + increasing doses of B using a 3+3 design in 3 parts: Part I (cohorts received low E doses); Part II (dose-escalation cohort for B [1−5.5mg/kg] + 1.4mg/m2 E); Ex…
Efficacy and Determinants of Response to HER Kinase Inhibition in HER2-Mutant Metastatic Breast Cancer
Abstract HER2 mutations define a subset of metastatic breast cancers with a unique mechanism of oncogenic addiction to HER2 signaling. We explored activity of the irreversible pan-HER kinase inhibitor neratinib, alone or with fulvestrant, in 81 patients with HER2-mutant metastatic breast cancer. Overall response rate was similar with or without estrogen receptor (ER) blockade. By comparison, progression-free survival and duration of response appeared longer in ER+ patients receiving combination therapy, although the study was not designed for direct comparison. Preexistent concurrent activating HER2 or HER3 alterations were associated with poor treatment outcome. Similarly, acquisition of m…