A Pilot Study of Liposomal Doxorubicin Combined with Bevacizumab followed by Bevacizumab Monotherapy in Patients with Advanced Kaposi Sarcoma
Mené sur 16 patients atteints d'un sarcome de Kaposi, associé ou non à une infection par le VIH, cet essai évalue l'efficacité, du point de vue du taux de réponse globale et de la survie sans progression, et la toxicité d'un traitement combinant doxorubicine liposomale et bévacizumab, suivi du bévacizumab dispensé en monothérapie
Purpose: Vascular endothelial growth factor A (VEGF-A) is important in the pathogenesis of Kaposi sarcoma (KS), and bevacizumab has response rate of 31%. We explored the combination of bevacizumab with liposomal doxorubicin in patients with KS. Experimental Design: KS patients requiring systemic therapy were enrolled in one of two cohorts. Cohort 1 included patients with human immunodeficiency virus (HIV)-negative KS or with HIV-associated KS who would not be expected to respond to antiretroviral therapy (ART) alone (i.e. either stable or progressive KS on ART). Cohort 2 included all other patients with HIV-associated KS. Patients were treated with 6 cycles of liposomal doxorubicin with bevacizumab every 3 weeks followed by up to 11 cycles of bevacizumab alone. Results: Sixteen patients were enrolled: 10 (2 HIV negative) in cohort 1 and 6 in cohort 2. Fourteen patients had advanced disease (AIDS Clinical Trials Group T1). Overall response rate (complete and partial responses) was 56% (80% CI, 38% to 74%) for all patients and were similar in the 2 cohorts. Median progression free survival was 6.9 months (95% CI of 4.5 months to not estimable). Grade 3 and 4 adverse events attributed to therapy included hypertension (n=5), neutropenia (n=6), gastrointestinal hemorrhage (n=1) and cerebral ischemia (n=1). There was a significant decrease in VEGF-A levels from baseline to the end of 6 cycles of combination therapy. Conclusions: Pegylated liposomal doxorubicin in combination with bevacizumab has activity in advanced KS, but it is unclear if the combination yields better outcomes than liposomal doxorubicin used alone.