Adding carotuximab to pazopanib does not improve progression-free survival (PFS) in patients with advanced angiosarcoma, according to results of the TAPPAS trial published in JAMA Oncology.
The phase 3 TAPPAS trial (ClinicalTrials.gov Identifier: NCT02979899) enrolled 128 patients with advanced angiosarcoma. They were randomly assigned to receive oral pazopanib (800 mg/day) alone or intravenous carotuximab (10 mg/kg weekly) with oral pazopanib (800 mg/day).
There were 114 evaluable patients, 53 in the pazopanib-alone arm and 61 in the carotuximab-pazopanib arm. The median age at baseline was 68 years (range, 24 to 82 years), 61% of patients were women, 50% had cutaneous disease, and 28% had no prior treatment.
At the data cutoff for the primary analysis (March 14, 2019), 50 patients in the pazopanib arm had withdrawn from the study, and 19 completed follow-up. In the carotuximab-pazopanib arm, 48 patients had withdrawn, and 18 completed follow-up.
The median PFS, by blinded independent review, was 4.3 months in the monotherapy arm and 4.2 months in the combination arm (hazard ratio [HR], 0.98; 95% CI, 0.52-1.84; P =.95). The objective response rate was 13% in the monotherapy arm and 5% in the combination arm (P =.09).
The median overall survival was 7.7 months in the pazopanib-alone arm and 10.9 months in the carotuximab-pazopanib arm (HR, 0.79; 95% CI, 0.41-1.51; P = .47).
The most common all-grade adverse events (AEs) were fatigue (55% in the monotherapy arm and 61% in the combination arm), headache (23% and 64%, respectively), diarrhea (51% vs 57%), nausea (49% vs 48%), vomiting (23% vs 38%), anemia (9.4% vs 44%), epistaxis (4% vs 56%), and hypertension (55% vs 36%).
Hypertension was the most common AE of grade 3 or higher in both arms (27% in the monotherapy arm and 19% in the combination arm). Other “notable” grade 3 or higher AEs, according to the researchers, were increased enzyme levels and decreased electrolyte levels.
“The study’s findings indicate that the combination of pazopanib plus carotuximab is not superior to pazopanib alone in treating patients with advanced angiosarcoma,” the researchers concluded.
Disclosures: This research was supported by TRACON Pharmaceuticals. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Jones RL, Ravi V, Brohl AS, et al. Efficacy and safety of TRC105 plus pazopanib vs pazopanib alone for treatment of patients with advanced angiosarcoma: A randomized clinical trial. JAMA Oncol. Published online March 31, 2022. doi:10.1001/jamaoncol.2021.3547