Efficacy and Safety of TRC105 + Pazopanib vs. Pazopanib Alone in Advanced Angiosarcoma Patients

Angiosarcoma is a rare subtype of sarcoma associated with a dismal prognosis. A phase 1/2 trial demonstrated that in pazopanib-naive patients with chemotherapy-resistant angiosarcoma, carotuximab combined with pazopanib resulted in a median progression-free survival (PFS) of 7.8 months. The study investigated whether carotuximab plus pazopanib can enhance PFS in patients with advanced angiosarcoma compared to pazopanib alone. The TAPPAS Trial was a phase 3 randomized clinical trial that evaluated the efficacy and safety of carotuximab plus pazopanib compared to pazopanib alone in patients with advanced angiosarcoma. Between February 16, 2017, and April 12, 2019, 123 patients with advanced angiosarcoma at least 18 years old were included in the trial at 31 sites in US and EU. Patients were randomly assigned to receive either pazopanib alone or pazopanib + carotuximab in a 1:1 ratio. The prosecution utilized an adaptive enrichment design, with inclusion criteria of no more than 2 prior lines of systemic therapy and an Eastern Cooperative Oncology Group performance status of 0 or 1.

Patients received oral pazopanib at 800 mg daily, intravenous carotuximab at 10 mg/kg administered weekly, and oral pazopanib at the same amount. Dose modification was allowed based on patient tolerance or until disease progression. The efficacy analysis utilized the intent-to-treat population, while the safety analysis included all patients who received a dose of either study drug. During the TAPPAS trial, the primary endpoint of PFS was evaluated using blinded independent radiographic and cutaneous photographic review following Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, version 1.1. The secondary goals were overall survival (OS) and objective response rate (ORR). An interim analysis was performed to determine the final sample size after 123 patients were enrolled. Using the log rank test, PFS was compared between the pazopanib alone and the carotuximab plus pazopanib group.

Of the 114 patients whose data were evaluated (53 in the pazopanib arm and 61 in the carotuximab plus pazopanib arm), 69 (61%) were female with a median age of 68 years (ranging from 24 to 82 years). About half of the patients, 57 (50%), had cutaneous disease, and 32 (28%) had not undergone prior treatment. The study did not reach its primary endpoint (progression-free survival) as (hazard ratio [HR], 0.98; 95% CI, 0.52-1.84; P = .95)), with a median of 4.3 months (95% CI, 2.9 months to not reached) for the pazopanib arm and 4.2 months (95% CI, 2.8-8.3 months) for the combination arm. Fatigue (29 patients [55%] vs. 37 [61%]) and headache (12 patients [23%] vs. 39 [64%]) were identified as the most frequently reported all-grade adverse event in both the single-agent pazopanib arm and the combination arm. After that, epistaxis (2 patients [4%] vs. 34 [56%]), diarrhea (27 patients [51%] vs. 35 [57%]), vomiting (12 patients [23%] vs. 23 [38%]), nausea (26 patients [49%] vs. 29 [48%]), anemia (5 patients [9%] vs. 27 [44%]), and hypertension (29 patients [55%] vs 22 [36%]).

The study concluded that adding carotuximab to pazopanib did not provide any benefits compared to pazopanib alone in patients with advanced angiosarcoma.

Source: https://pubmed.ncbi.nlm.nih.gov/35357396/

Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT02979899

Jones RL, Ravi V, Brohl AS, Chawla S, Ganjoo KN, Italiano A, Attia S, Burgess MA, Thornton K, Cranmer LD, Cheang MCU, Liu L, Robertson L, Adams B, Theuer C, Maki RG. Efficacy and Safety of TRC105 Plus Pazopanib vs. Pazopanib Alone for Treatment of Patients With Advanced Angiosarcoma: A Randomized Clinical Trial. JAMA Oncol. 2022 May 1;8(5):740-747. doi: 10.1001/jamaoncol.2021.3547. PMID: 35357396; PMCID: PMC8972152.