In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 2074-2074
Abstract:
2074^ Background: Prognosis of recurrent MG remains poor with a median survival of 3-9 months. Few evidence based treatments are available and response rates have been 〈 20% with 6 month progression–free survival (PFS) of 〈 9-16%. Poor prognosis is linked to the MG’s ability to induce vascular proliferation and invasion. MG’s have an abundance of neo-vascularization and high levels of vascular endothelial growth factor (VEGF). BEV, an antibody to VEGF, is the most active agent tested for recurrent MG with an overall response rate of 21.2%. Rilotumumab is a human monoclonal antibody that blocks human hepatocyte growth factor (HGF) and its receptor c-Met. HGF/c-Met signaling plays a role in MG tumorigenicity inducing angiogenesis and expression of additional angiogenic autocrine factors such as VEGF. The novel combination of rilotumumab (C-Met inhibitor) with an anti-VEGF drug (BEV) to block vascular invasion and tumor proliferation may demonstrate synergistic tumor growth inhibition. Methods: A two-stage design is used to assess radiographic response rate with 〉 3 responses required for the first stage. Secondary endpoints were PFS, overall survival (OS) and toxicity. Subjects with recurrent BEV-naïve MGs received rilotumumab at 20 mg/kg in combination with BEV at 10 mg/kg every two weeks ≥ 28 days after the last surgical procedure. A brain MRI was obtained after each 6-week cycle. Results: 15 of the 19 patients required for the first stage have been accrued. 10(67%) were male and ≥ 50 years. 73% received ≥ 2 prior regimens and 46% had ≥ 2 prior progressions. Best tumor response included 1(7%) complete response, 2 (13%) partial responses, 8 (53%) stable disease, 1 (7%) progressive disease with 20% (3/15) non-evaluable due to early termination secondary to toxicity. Median PFS was 3.9 months (95% CI: 1, 7.1) with a 6-month PFS of 25.4% (95% CI: 6.4, 50.5) and 6-month OS of 68.3% (95% CI: 34, 87.1). Toxicities are listed below. Maximum average weight increase over all cycles was 6.3 % (SD ± 6.09). Conclusions: Rilotumumab in combination with BEV is an active regimen in MG. Toxicity will need to be closely monitored. [Table: see text]
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2012.30.15_suppl.2074
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2012
detail.hit.zdb_id:
2005181-5
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