Adding pazopanib to preoperative chemoradiotherapy highly active in soft-tissue sarcoma
Adding pazopanib to neoadjuvant chemoradiotherapy significantly increased the rate of pathologic near-complete response in patients with large intermediate- or high-grade soft-tissue sarcoma, according to an article in The Lancet Oncology.
In this multicenter open-label trial, 81 adults or children with newly diagnosed trunk or extremity chemotherapy-sensitive soft-tissue sarcoma > 5 cm in diameter were randomly assigned to receive preoperative chemoradiotherapy with or without pazopanib (350 mg/m2 once daily in children and at 600 mg once daily in adults). Pazopanib was started during the first cycle of chemotherapy and continues during pre- and postoperative treatment with the exception of the 7-days prior to surgery and the 14-days after surgery.
Ifosfamide and doxorubicin were given at 3-week intervals. Radiotherapy began at the start of the second cycle of chemotherapy, followed by surgical resection at week 13.
A 90% pathologic response or higher was noted in 58% and 22% of patients in the pazopanib group and control group, respectively. At week 13 prior to surgery, radiographic evaluation showed a partial response or better in 52% and 58% of patients in the pazopanib group and control group, respectively.
The authors concluded: “In this presumed first prospective trial of soft tissue sarcoma spanning nearly the entire age spectrum, adding pazopanib to neoadjuvant chemoradiotherapy improved the rate of pathological near complete response, suggesting that this is a highly active and feasible combination in children and adults with advanced soft tissue sarcoma. The comparison of survival outcomes requires longer follow-up.”
Weiss AR, Chen YL, Scharschmidt TJ, 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, randomised, open-label, phase 2 trial. Lancet Oncology. 2020; DOI:https://doi.org/10.1016/S1470-2045(20)30325-9.