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

Ramya Ramaswami*, Thomas S. Uldrick, Mark N. Polizzotto, Kathleen M. Wyvill, Priscila Goncalves, Anaida Widell, Kathryn Lurain, Seth M. Steinberg, William Douglas Figg, Giovanna Tosato, Denise Whitby, Robert Yarchoan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)4238-4247
Number of pages10
JournalClinical Cancer Research
Volume25
Issue number14
DOIs
StatePublished - 2019
Externally publishedYes

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