Carotuximab addition to pazopanib does not improve survival in advanced angiosarcoma patients

1. Carotuximab in tandem with pazopanib did not show improvement in progression-free survival or overall survival than pazopanib alone

2. Some of the most common adverse events of any grade across both groups were fatigue, hypertension, diarrhea, and nausea.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Angiosarcoma is a rare and aggressive subtype of sarcoma, with limited treatment options in its more advanced stages. This study explored carotuximab (an endoglin pathway inhibitor) and pazopanib (a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor), and their efficacy and safety on patients with advanced angiosarcoma. These patients were randomly assigned to receive either panzopanib or carotuximab plus panzopanib. The study also used an adaptive enrichment design with interim data analysis. Median overall survival (OS) and median progression-free survival (PFS) were not significantly different between both groups. More toxic effects were linked to the combination group than the control group. Anemia and fatigue had a higher occurrence in the combination group compared to pazopanib alone, while hypertension was the most common adverse event across both groups. Other common adverse events of any grades across both groups include fatigue, diarrhea, and nausea. The strengths of this study include its limited bias given its design and that it was able to show non-superiority of the combination group compared to panzopanib alone. The study is limited by the heterogenous nature of angiosarcomas and the small sample size for a phase 3 clinical trial. Overall, this study demonstrated that carotuximab plus panzopanib is not more efficacious nor safer than panzopanib alone in patients with advanced angiosarcoma.

Click to read the study in JAMA Oncology

Relevant Reading: Current management of angiosarcoma: recent advances and lessons from the past

In-Depth [randomized control trial]: This phase III international, parallel-group, randomized control trial included 123 patients with advanced angiosarcoma. They were randomly assigned in a 1:1 ratio to receive either panzopanib or carotuximab plus panzopanib; 61 were in the control group and 62 were in the combination group, with 50% of patients having cutaneous angiosarcoma. Median OS was 7.7 months in the control group and 10.9 months in the combination group (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.41 to 1.51; P=0.47). In patients with cutaneous angiosarcoma, median OS was 8 months and was not reached, respectively (n = 63; HR, 0.68; 95% CI, 0.25 to 1.84; p = 0.45). Median PFS was 4.3 months and 4.2 months, respectively (HR, 0.98; 95% CI, 0.52 to 1.84; p = 0.95), while in patients with cutaneous angiosarcoma it was 5.6 months and 4.2 months, respectively (n = 64; HR, 1.07; 95% CI, 0.43 to 2.67; p = 0.89). Anemia and fatigue occurred more frequently in the combination group, with a 23% and 12% increase, respectively. Other common adverse events of any grade in the control group vs. the combination group, respectively, were diarrhea (51% vs. 57%), nausea (49% vs. 48%), and hypertension (55% vs. 36%). Overall, this study demonstrated that carotuximab plus panzopanib did not improve efficacy nor safety in comparison to panzopanib alone in patients with advanced angiosarcoma.

Image: PD

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