The addition of pazopanib to neoadjuvant chemoradiotherapy in children and adults with soft tissue sarcoma improved the rate of pathological near complete response, a new study showed.

In fact, the rate of pathological near complete response more than doubled. At a second planned interim analysis that included 42 evaluable patients, 58% of patients assigned to receive pazopanib had 90% pathological response or higher compared with 22% in patients in the control group. Based on this result, the study was stopped.

“We anticipate that the findings of this study might change the approach to advanced, unresected soft tissue sarcomas in children and adults and encourage additional joint pediatric and adult studies in soft tissues sarcoma and other disease that extend across age boundaries in the future,” the researchers wrote. “It will be important to determine whether greater pathological response rate will translate into improved local control and survival.”

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The trial was a combined effort from Children’s Oncology Group and NRG Oncology. It enrolled adults and children from 57 hospitals in the United States and Canada with newly diagnosed, unresected trunk or extremity soft tissue sarcomas larger than 5 cm in diameter.

Patients received ifosfamide and doxorubicin with 45 Gy preoperative radiotherapy followed by surgical resection at week 13. Patients were randomly assigned to receive oral pazopanib or be in the control group.

The researchers noted that historically, the pathological response rate in this disease are between 30% and 50%. At the predetermined interim analysis looking at 37 patients, the median pathological response was 95% for patients assigned to receive pazopanib and 50% for those in the control group.

Common grade 3/4 adverse events included leukopenia (43%), neutropenia (41%), and febrile neutropenia (41%) in patients assigned pazopanib, and neutropenia (9%) and febrile neutropenia (9%) in the control group.

The majority (59%) of patients assigned pazopanib also had a serious treatment-related adverse event.


Weiss AR, Scharschmidt TJ, Chi YY, et al. Pathological response in children and adults with large unresected intermediate-grade or high-grade soft tissue sarcoma receiving preoperative chemoradiotherapy with or without pazopanib (ARST1321): a multicentre, randomized, open-label, phase 2 trial [published online July 20, 2020]. Lancet Oncol. doi: 10.1016/S1470-2045(20)30325-9