In the phase III TAPPAS trial reported in JAMA Oncology, Jones et al found that the addition of carotuximab to pazopanib did not improve progression-free survival in patients with advanced angiosarcoma.
Carotuximab is an IgG1 antibody that binds endoglin, which is highly expressed on proliferating endothelial cells. As noted by the investigators, preclinical data suggest that targeting the endoglin and VEGF pathways concurrently may lead to more effective angiogenesis inhibition.
The open-label trial included 114 evaluable patients from sites in the United States and Europe. They were randomly assigned between February 2017 and April 2019 to receive carotuximab at 10 mg/kg weekly plus pazopanib at 800 mg/day (n = 61) or pazopanib at 800 mg/day (n = 53) until disease progression or unacceptable toxicity. Patients could have received no more than two prior lines of systemic therapy; overall, 28% of patients had no prior treatment. A total of 31 patients (51%) in the combination group and 26 (49%) in the control group had cutaneous disease. The primary endpoint was progression-free survival on blinded independent radiographic and cutaneous photographic review.
Pazopanib dose reductions were required by 59% of patients in the combination group and 60% of patients in the control group.
Median progression-free survival was 4.2 months (95% confidence interval [CI] = 2.8–8.3 months) in the combination group vs 4.3 months (95% CI = 2.9 months–not reached) in the control group (hazard ratio [HR] = 0.98, 95% CI = 0.52–1.84, P = .95). Among patients with cutaneous disease, median progression-free survival was 4.2 months (95% CI = 2.8–8.3 months) vs 5.6 months (95% CI = 2.6–5.6 months; HR = 1.07, 95% CI = 0.43–2.67, P = .89).
Median overall survival was 10.9 months (95% CI = 6.8 months–not reached) in the combination group vs 7.7 months (95% CI = 6.8 months–not reached) in the control group (HR = 0.79, 95% CI = 0.41–1.51, P = .47). Among patients with cutaneous disease, median overall survival was not reached (95% CI = 6.8 months–not reached) vs 8.0 months (95% CI = 6.7 months–not reached; HR = 0.68, 95% CI = 0.25–1.84, P = .45).
The most common adverse events of any grade in the combination group were headache (64% vs 23% in control group), fatigue (61% vs 55%), and diarrhea (57% vs 51%). The most common grade ≥ 3 adverse events in the combination group were anemia (27%), hypertension (19%), fatigue (14%), and nausea (11%). The most common in the control group were hypertension (27%), increased alanine aminotransferase (13%), and increased aspartate aminotransferase (9%).
The investigators concluded: “In this phase III randomized clinical trial, carotuximab plus pazopanib did not improve progression-free survival compared with pazopanib alone in patients with advanced angiosarcoma.”
Robin L. Jones, MD, of the Sarcoma Unit, Royal Marsden Hospital and Institute of Cancer Research, London, is the corresponding author for the JAMA Oncology article.
Disclosure: The trial was funded by TRACON Pharmaceuticals. For full disclosures of the study authors, visit jamanetwork.com.