Paper # 31|
A Phase II Study Targeting Vascular Endothelial Growth Factor with the Humanized Monoclonal Antibody Bevacizumab in the Treatment of Patients with HIV-associated Kaposi Sarcoma
Thomas Uldrick*, K Wyvill, P Kumar, W Bernstein, D O’Mahony, M Polizzotto, S Steinberg, S Pittaluga, R Little, and R Yarchoan
NCI, Bethesda, MD, US
Background: Kaposi sarcoma (KS) is a complex tumor
consisting of proliferative spindle cells, abnormal vascularization and
inflammatory cells. It is caused by Kaposi sarcoma-associated herpes virus.
Vascular endothelial growth factor (VEGF) autocrine and paracrine signaling is
important in the pathogenesis of KS. We evaluated humanized anti-VEGF antibody,
bevacizumab, in the treatment of patients with HIV-associated KS (HIV-KS).
Methods: A phase II study was conducted in
patients with biopsy-confirmed KS. Patients were stratified by HIV status.
HIV-infected patients were eligible if they had progressive KS while on
combination antiretroviral therapy (cART) for at least 1 month, or KS that had
not regressed despite optimized cART for at least 4 months. Bevacizumab 15 mg/kg
was administered intravenously on day 1 (loading dose) and day 8 of the first
cycle, and every 3 weeks thereafter. The primary objective was to assess
anti-tumor effect, using modified ACTG criteria, in patients with HIV-KS.
Safety and toxicity were monitored using CTCAE v2.0.
Results: Baseline patient characteristics
were as follows: 17 patients enrolled, 16 men, 1 woman; 8 black, 6 white, 3
Hispanic;, median age 44 (23 to 65) years; 76% had advanced disease (ACTG T1),
median CD4 294 [7 to 654], 41% had CD4 <200, median HIV viral load <50
[<50 to 180,000]. Patient response included the following: Patients received
a median of 10 (1 to 37) cycles, and were followed for median 8.4 (3-37] months.
In addition, 16 of 17 were assessable for tumor response. Best responses
observed: complete response (CR) 2/16 (12%), partial response (PR) 3/16 (19%),
stable disease (SD) 9/16 (56%), and progressive disease (PD) 2/16 (12%).
Overall response rate (CR + PR) was 31% (95% confidence interval, 11% to 58.7%).
One patient achieved a durable CR after initial transient progression. One
patient had rapid resolution of a chylous effusion. In patients with PR or CR,
median time to best response was 5 (1 to 7.5) months. Median time to
progression was 7.5 months. Of a total 193 cycles administered, number of
cycles with grade 3 to 4 adverse events at least possibly attributed to therapy
included: hypertension (6), headache (2), vomiting (1), neutropenia (3), and cellulitis
Conclusions: These results support the strategy of
targeting VEGF with bevacizumab in the treatment of HIV-KS. This approach may
add to the therapeutic options for patients with advanced or difficult to
manage KS. Evaluation of bevacizumab combined with liposomal doxorubicin is