Data from A Pilot Study of Liposomal Doxorubicin Combined with Bevacizumab followed by Bevacizumab Monotherapy in Patients with Advanced Kaposi Sarcoma

Abstract

<div>AbstractPurpose:<p>VEGF-A is important in the pathogenesis of Kaposi sarcoma, and bevacizumab has a response rate of 31%. We explored the combination of bevacizumab with liposomal doxorubicin in patients with Kaposi sarcoma.</p>Patients and Methods:<p>Patients with Kaposi sarcoma requiring systemic therapy were enrolled in one of two cohorts. Cohort 1 included patients with human immunodeficiency virus (HIV)-negative Kaposi sarcoma or with HIV-associated Kaposi sarcoma who would not be expected to respond to antiretroviral therapy (ART) alone (i.e., either stable or progressive Kaposi sarcoma on ART). Cohort 2 included all other patients with HIV-associated Kaposi sarcoma. Patients were treated with six cycles of liposomal doxorubicin with bevacizumab every 3 weeks followed by up to 11 cycles of bevacizumab alone.</p>Results:<p>Sixteen patients were enrolled: 10 (two HIV negative) in cohort 1 and six in cohort 2. Fourteen patients had advanced disease (AIDS Clinical Trials Group T<sub>1</sub>). Overall response rate (complete and partial responses) was 56% [80% confidence interval (CI), 38%–74%] for all patients and were similar in the two cohorts. Median progression-free survival was 6.9 months (95% CI, 4.5 months–not estimable). Grade 3 and 4 adverse events attributed to therapy included hypertension (<i>n</i> = 5), neutropenia (<i>n</i> = 6), gastrointestinal hemorrhage (<i>n</i> = 1), and cerebral ischemia (<i>n</i> = 1). There was a significant decrease in VEGF-A levels from baseline to the end of six cycles of combination therapy.</p>Conclusions:<p>Pegylated liposomal doxorubicin in combination with bevacizumab has activity in advanced Kaposi sarcoma, but it is unclear whether the combination yields better outcomes than liposomal doxorubicin used alone.</p></div>