A pilot study of liposomal doxorubicin combined with bevacizumab followed by bevacizumab monotherapy in patients with advanced kaposi sarcoma

Purpose: 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. Patients and Methods: 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. Results: 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 T₁). 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 (n ¼ 5), neutropenia (n ¼ 6), gastrointestinal hemorrhage (n ¼ 1), and cerebral ischemia (n ¼ 1). There was a significant decrease in VEGF-A levels from baseline to the end of six cycles of combination therapy. Conclusions: 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.