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An In Vitro Model for Studying Cellular Transformation by Kaposi Sarcoma Herpesvirus
Published on: August 25, 2017
Treatment With PD-1/PD-L1 Inhibitors for Kaposi Sarcoma:A Systematic Review and Meta-Analysis
Francisco Cezar Aquino de Moraes1, Michele Kreuz2, Pedro Henrique de Souza Wagner3
1Federal University of Pará, Belém, Pará, Brazil.
Abstract:
Kaposi Sarcoma (KS) is an angioproliferative tumor induced by human gammaherpesvirus 8 (HHV-8). For years, cytotoxic chemotherapy was the primary treatment for advanced KS, despite high toxicity and limited efficacy. Immunotherapy, particularly PD-1/PD-L1 inhibitors, has emerged as a promising option with antitumor activity and a favorable safety profile. We conducted a meta-analysis to evaluate its efficacy and safety in KS. A systematic search in Medline, Embase, Cochrane Library, and Web of Science identified single-arm trials on PD-1/PD-L1 inhibitors in KS. Outcomes were expressed as proportions with 95% CIs, heterogeneity assessed using I ², and significance set at P <0.05. Analyses were performed in RStudio 4.4.1. Five studies with 91 patients were included. Prior treatments included chemotherapy (35.0%), radiotherapy (22.3%), and interferon (9.2%). The pooled objective response rate (ORR) was 61% (95% CI: 49-72; I ²=16%), with 17% achieving complete response (CR) (95% CI: 8-31; I ²=0%), and the disease control rate (DCR) was 91% (95% CI: 81-96; I ²=0%). The most frequent adverse events (AEs) were pruritus (42%; 95% CI: 16-73; I ²=74%), fatigue (27%; 95% CI: 8-60; I ²=67%), and arthralgia (14%; 95% CI: 5-37; I ²=60%). This meta-analysis supports the antitumor activity of PD-1/PD-L1 inhibitors in KS. Despite high AE rates, most were clinically manageable.
Insights
PD-1/PD-L1 inhibitors show significant antitumor activity for Kaposi Sarcoma (KS), a tumor caused by human gammaherpesvirus 8 (HHV-8). While adverse events like pruritus and fatigue are common, they are generally manageable, offering a promising alternative to chemotherapy.
Area of Science:
- Oncology
- Immunology
- Virology
Background:
- Kaposi Sarcoma (KS) is an angioproliferative tumor linked to human gammaherpesvirus 8 (HHV-8).
- Traditional chemotherapy for advanced KS presents challenges due to toxicity and limited effectiveness.
- Immune checkpoint inhibitors, specifically PD-1/PD-L1 inhibitors, represent a novel therapeutic avenue with potential antitumor benefits and improved safety profiles.
Purpose of the Study:
- To conduct a meta-analysis evaluating the efficacy and safety of PD-1/PD-L1 inhibitors in patients with Kaposi Sarcoma.
- To synthesize data from existing single-arm trials to provide a comprehensive overview of treatment outcomes.
- To compare the effectiveness and tolerability of immunotherapy against conventional KS treatments.
Main Methods:
- Systematic literature search across major databases (Medline, Embase, Cochrane Library, Web of Science).
- Inclusion of single-arm trials investigating PD-1/PD-L1 inhibitors for Kaposi Sarcoma.
- Statistical analysis of outcomes including objective response rate (ORR), complete response (CR), disease control rate (DCR), and adverse events (AEs) using proportions and 95% confidence intervals (CIs). Heterogeneity was assessed using I².
Main Results:
- Five studies involving 91 patients were analyzed, with prior treatments including chemotherapy, radiotherapy, and interferon.
- The pooled objective response rate (ORR) was 61% (95% CI: 49-72%), with a 17% complete response (CR) rate (95% CI: 8-31%).
- The disease control rate (DCR) reached 91% (95% CI: 81-96%). Common adverse events included pruritus (42%), fatigue (27%), and arthralgia (14%), which were mostly manageable.
Conclusions:
- PD-1/PD-L1 inhibitors demonstrate significant antitumor activity in Kaposi Sarcoma.
- The immunotherapy approach offers a viable alternative to traditional chemotherapy for advanced KS.
- While adverse events are frequent, they are generally clinically manageable, supporting the use of these agents in KS treatment.
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