In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. e21139-e21139
Abstract:
e21139 Background: At ASCO 2011 we presented safety and efficacy results from a phase I study of L in combination with S in patients with solid tumors refractory to standard therapy (NCT00984425). To investigate potential biomarkers of biological activity of this combination, we analyzed serum levels of a panel of soluble proteins characterizing the oncogenic signalling pathways targeted by L and S (VEGF, sVEGFR-2, EGF, sEGFR, sHER2/neu), and others mediators of angiogenesis such as sPDGFR, IL-8, IL-6, bFGF, PIGF, TGF-α e β, HGF. Methods: Serum samples from 22/30 patients enrolled in this trial were prospectively collected at baseline and then every two months until treatment discontinuation. Serum levels of VEGF, sVEGFR-2, EGF, sEGFR, sHER2/neu and sPDGFR were measured via enzyme-linked immunoadsorbent assays analysis (ELISA). Possible correlations between serum proteins levels and disease-control rate (SCR), PFS or OS were assessed by logistic and Cox regression model, respectively. Results: Analysis of baseline biomarkers as a function of demographic variables indicated that VEGF levels were inversely correlated with age (P= .018) and VEGFR-2 was significantly associated with tumor burden (P= .037). Risk of progression increased with high baseline sEGFR levels (HR 1.10; p= .0498). Overall, PD changes suggest that treatment with L and S increased VEGF and sHER2/neu levels, while decreased EGF, sEGFR, VEGFR-2 and sPDGFR. Mainly, sEGFR levels decreased by at least 75% at the first radiological assessment in half of patients, whereas at the end of treatment a reduction ≥80% was observed in 18 patients; a greater reduction of sEGFR levels was significantly associated with a higher risk of progression (HR 8.3; P 〈 .01) and death (HR 3.6; P= .023). An increase of VEGF levels during treatment seemed to be associated with better SCR (OR: 6.33; P= .085). Conclusions: In this small subset of patients treated with L and S a significant modulation of serum biomarkers was observed. The clinical significance of these changes as potential surrogate markers requires further evaluation. Data concerning other angiogenic markers along with tissue analysis (IHC, FISH and mutation) will be presented at the meeting.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2012.30.15_suppl.e21139
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2012
detail.hit.zdb_id:
2005181-5
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