Canadian Cancer Trials Group IND197: a phase II study of foretinib in patients with estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2-negative recurrent or metastatic breast cancer.

摘要: In murine models, overexpression of the MET receptor transgene induces tumors with human basal gene expression characteristics supporting inhibition as a treatment strategy for triple-negative breast cancer (TNBC). Foretinib is an oral multi-kinase inhibitor MET, RON, AXL, TIE-2, and VEGF receptors anti-tumor activity in advanced HCC papillary renal cell cancer. Patients centrally reviewed primary TNBC 0–1 prior regimens metastatic disease received daily foretinib 60 mg po 2-stage single-arm trial. Primary endpoints were objective response early progression rates per RECIST 1.1. stage 2, correlative studies PTEN, EGFR, p53 on archival fresh tumor specimens performed along enumeration CTCs. 45 patients enrolled 37 having evaluable confirmed (cTNBC). There 2 partial responses (ITT 4.7 % cTNBC 5.4 %) median duration 4.4 months (range 3.7–5 m) 15 had stable 33 %, 40.5 %) 5.4 months 2.3–9.7 m). The most common toxicities (all grades/grade 3) nausea (64/4 %), fatigue (60/4 %), hypertension (58/49 %), diarrhea (40/7 %). Six serious adverse events considered possibly related to foretinib 4 went off study due events. was no correlation between positivity nor p53, or Although CCTG IND 197 did not meet its endpoint, observation clinical benefit rate 46 % this population suggests that may have single, non-cytotoxic agent (ClinicalTrials.gov number, NCT01147484).