Prognostic and predictive factors for angiosarcoma patients receiving paclitaxel once weekly plus or minus bevacizumab: an ancillary study derived from a randomized clinical trial

Abstract

BackgroundWe report here a correlation analysis conducted along with a phase II trial assessing bevacizumab in combination with weekly paclitaxel.MethodsCirculating pro/anti-angiogenic factors were assessed on day 1 (D1) and day 8 (D8). The prognostic value for progression-free survival (PFS) was evaluated using a Cox model with biomarkers as continuous variables.ResultsAmong the 51 patients enrolled and treated in this trial, biomarker analysis was performed for 42: 18 in Arm A (single-agent) and 24 in Arm B (combination). With a median follow-up of 46 months, PFS was 5.5 versus 5.7 months, respectively (p = 0.75). According to univariate analysis, factors associated with a poor PFS were as follows: visceral angiosarcoma, de novo angiosarcoma, and high PlGF and low VEGF-C baseline values. In multivariate analysis, de novo angiosarcoma (HR = 2.5; p = 0.024) and baseline VEGF-C value (HR = 0.7; p = 0.003) were significant prognostic factors. We observed a significant increase in circulating PlGF (< 0.001) and a decrease in VEGF (< 0.001) during bevacizumab treatment. An increase in FGF was associated with a poor outcome.ConclusionsDe novo angiosarcoma and a low baseline level of VEGF-C were found to be associated with a poor prognosis. Addition of bevacizumab induces major changes in circulating biomarkers (VEGF and PlGF) in a short timeframe without impacting PFS.Trial registrationRetrospectively registered on EudraCT N° 2009–017020-59 and NCT01303497 (February 24, 2011).Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4828-1) contains supplementary material, which is available to authorized users.

Plasminogen activating inhibitor‐1 promotes angiogenesis in cutaneous angiosarcomas

“…In addition to IL‐23p19, PAI‐1 also increased the mRNA expressions of VEGF‐C, CXCL5 and CCL20 on ISO‐HAS‐B angiosarcoma cells. Notably, angiosarcomas overexpress multiple VEGF receptors (VEGFRs) including VEGFR‐3, 33 and increased VEGF‐C expression correlates with cell proliferation in CAS 34 . Another report suggested that baseline VEGF‐C was associated with a poor prognosis of de novo angiosarcoma 35 .…”

Clinical implications of systemic and local immune responses in human angiosarcoma

“…The response rate to combination therapy was not only lower (29% vs 46%), these patients also experienced more frequent severe toxicities 31 . The evaluation of circulating pro/anti-angiogenic factors did not identify any subgroup that benefited from the addition of bevacizumab 41 . More recently, TRC105, an antibody against an essential angiogenic receptor known as endoglin, did not demonstrate significant activity when combined with pazopanib, a tyrosine kinase inhibitor with anti-angiogenic activity 42 .…”

Soft Tissue Epithelioid Vascular Tumors: A Practical Clinico Pathological Diagnostic Approach

“…However, no significant difference in PFS between treatment groups is reported. Unfortunately, even in combination with target agents such as bevacizumab response rates remained disappointing ( 92), (93)(94)(95).…”