Abstract 3841: Bevacizumab (BEV) and risk of arterial (ATE) and venous thromboembolism (VTE) in metastatic castration-resistant prostate cancer (mCRPC) patients treated on CALGB 90401(ALLIANCE)
Authors: Patel Jai N. , Jiang Chen , Hertz Daniel L. , Mulkey Flora A. , Friedman Paula N. , Halabi Susan , Ratain Mark J. , Morris Michael J. , Small Eric J. , Owzar Kouros , Kelly William K. , McLeod Howard L. 
Published: May 2015

Background BEV is associated with an increased risk of ATE, however, its effect on VTE remains controversial. We investigated the association of BEV treatment and clinical risk factors with the incidence of ATE and VTE in a large randomized phase III study.

Methods mCRPC patients were randomized to receive docetaxel and prednisone with or without BEV once every 21 days. Competing risks cycle-to-event Cox regression models were used to investigate the association of BEV on the incidence of grade 3 or higher (3+) ATE (“cardiac ischemia/infarction” or “CNS ischemia”) and VTE (“thrombosis/thrombus/embolism”). Age, prior ATE/VTE, baseline antiplatelet/anticoagulant and VTE risk score were evaluated in univariable and multivariable analyses.

Results The analysis included 800 patients. The odds of experiencing grade 3+ ATE was significantly greater in BEV treated patients compared to placebo (OR 4.16, P=0.006; 4.02% [16/398] and 1.00% [4/402], respectively). The odds of experiencing grade 3+ VTE was lower in BEV treated patients compared to placebo (OR=0.57, P=0.08; 4.52% [18/398] and 7.71% [31/402], respectively). In the multivariable analysis, BEV treatment (HR=4.28; P=0.009) and prior ATE (HR=2.71; P=0.047) were associated with increased ATE, while age (HR=1.05; P=0.009) and VTE risk score (HR=2.24; P=0.007), but not BEV treatment (HR=0.62; P=0.11), were associated with increased VTE (Table 1).

Conclusion Due to the lack of survival benefit noted in the clinical trial, these results further reinforce the recommendation for not using BEV in this patient population, as it also placed patients at a significantly greater risk for ATE. However, the influence on VTE, if any, was a decreased risk. Understanding the risk factors for ATE and VTE is essential to mitigate risks and reduce the burden of these prevalent complications in cancer care.

Table 1 Risk of ATE and VTE by treatment arm and clinical risk factors

Table 1Risk of ATE and VTE by treatment arm and clinical risk factorsATERisk factorVTECause-specific HRCause-specific HR(95% CI)(95% CI)P-valueP-valueMultivariableUnivariableUnivariableMultivariable4.283.96BEV treatment0.560.62(1.42-12.84)(1.32-11.85)(0.31-1.00)(0.35-1.12)0.0090.0140.0510.111.051.05Agea1.041.05(0.99-1.11)(1.00-1.11)(1.01-1.08)(1.01-1.09)0.120.070.020.0092.713.48Prior thrombosis1.030.97(1.01-7.26)(1.33-9.07)(0.25-4.26)(0.23-4.07)0.0470.010.960.971.631.87Baseline antiplatelet/ anticoagulant 0.940.82(0.62-4.27)(0.72-4.86)(0.53-1.67)(0.46-1.47)0.320.20.850.51N/AN/AVTE risk scoreb2.012.24(1.14-3.54)(1.25-4.01)0.0150.007aAge as a continuous variablebLow, intermediate, or high risk if 0, 1-2, or ≥ 3 risk factors (hemoglobin &lt; 10 g/dL, platelet count ≥ 350,000/µl, leukocyte count &gt; 11,000/µl, body mass index ≥ 35 kg/m2), respectively; low vs. intermediate/high.

Citation Format: Jai N. Patel, Chen Jiang, Daniel L. Hertz, Flora A. Mulkey, Paula N. Friedman, Susan Halabi, Mark J. Ratain, Michael J. Morris, Eric J. Small, Kouros Owzar, William K. Kelly, Howard L. McLeod. Bevacizumab (BEV) and risk of arterial (ATE) and venous thromboembolism (VTE) in metastatic castration-resistant prostate cancer (mCRPC) patients treated on CALGB 90401(ALLIANCE). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3841. doi:10.1158/1538-7445.AM2014-3841