A multicenter, open-label phase II trial of dovitinib, an FGFR1 inhibitor, in FGFR1 amplified and non-amplified metastatic breast cancer.

作者：Fabrice André, Thomas Bachelot, Mario Campone, F. Dalenc, J. M. Perez-Garcia, SA Hurvitz, Nicholas C. Turner, H. S. Rugo, M. Shi, Yan Zhang, AC Kay, Alejandro Yovine, José Baselga · 发表于：Journal of Clinical Oncology · 年份：2011 · DOI：10.1200/jco.2011.29.15_suppl.508 · 被引用次数：32 · 研究领域：Fibroblast Growth Factor Research、Cancer Diagnosis and Treatment、Kruppel-like factors research

508 Background: Amplification of the FGFR1 gene occurs in ≈ 10% of breast cancers (BC), correlates with FGFR1 overexpression, and is mainly observed in ER+/Her2− BCs. Preclinical (pc) studies suggest that FGFR1 is a candidate therapeutic target in BC. Dovitinib (TKI258) is a tyrosine kinase inhibitor that targets FGFR, VEGFR, and PDGFR. In pc models, dovitinib demonstrated potent antitumor activities in FGFR1−amplified tumor cell lines. Methods: A 2-stage, phase 2 study to determine the efficacy and safety of dovitinib in 4 groups (gps) of metastatic BC patients (pts): (gp 1: FGFR1+, HR+), (gp 2: FGFR1+, HR−) (gp 3: FGFR1−, HR+), (gp 4: FGFR1−, HR−). Pt selection was performed according to FISH/CISH for FGFR1 (cut-off ≥ 6 gene copies). Dovitinib (500 mg) was administered once daily on a 5-day on/ 2-day off schedule. The primary endpoint was RECIST best overall response rate in pts with measurable disease per external radiology review. Results: As of January 2011, 81 pts were treated, with data for 77 pts available (gp 1 = 21, gp 3 = 34, gp 4 = 22). Prior therapy in the metastatic setting: a median of 2 chemotherapy lines (all pts) and 2 endocrine therapy lines (HR+ pts). 58% of pts had liver metastases (gp1: 81%; gps 3,4: 50%). Most common adverse events included: vomiting (75%; grade 3 [g3]: 6%), diarrhea (72%; g3: 6%), nausea (62%; g3: 5%), and asthenia (61%; g3: 17%). Median exposure was 1.7 (range, 0-8.2) months (mos), including 8 pts who received > 4 mos of therapy. For ...