Angiogenesis- and Hypoxia-Associated Proteins as Early Indicators of the Outcome in Patients with Metastatic Breast Cancer Given First-Line Bevacizumab-Based Therapy

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Siu W LamATX Trial Team

Abstract

We examined whether pretreatment levels of angiogenesis- or hypoxia-related proteins and their changes after one cycle of first-line bevacizumab-based therapy were associated with response, PFS, or OS in patients with metastatic breast cancer. We included 181 patients enrolled in the phase II ATX trial evaluating first-line paclitaxel and bevacizumab without or with capecitabine (NTR1348). Plasma samples were analyzed for VEGF-A, soluble VEGFR2 (sVEGFR2), angiopoietin 2 (ANG2), soluble TIE2 (sTIE2), IL6, IL8, and carbonic anhydrase 9 (CA9). Baseline serum CA15-3 was documented. HR was adjusted for confounding factors. Where appropriate, an optimal cut-off value defining a high and a low group was determined with Martingale residuals. At baseline, multiple proteins were significantly associated with PFS (ANG2, IL6, IL8, CA9, CA15-3) and OS (ANG2, sTIE2, IL6, IL8, CA9, CA15-3). After one cycle, VEGF-A, ANG2, sTIE2, and IL8 significantly decreased, while sVEGFR2 and CA9 significantly increased. The relative change in sVEGFR2 (P= 0.01) and IL8 (P= 0.001) was associated with response. Defining optimal cut-off, patients with a high CA9 rise (>2.9%) had better PFS (HR 0.45) and OS (HR 0.54) than those with low/no rise. Multiple angiog...Continue Reading

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Citations

Mar 27, 2018·British Journal of Cancer·Isabel Quiros-GonzalezSarah E Bohndiek
Jul 26, 2019·BMC Cancer·Leena TiainenPirkko-Liisa Kellokumpu-Lehtinen
Jul 7, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Shigeto UedaIchiei Kuji
May 27, 2021·The Cochrane Database of Systematic Reviews·Siao-Nge HoonAndrew D Redfern

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