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

• Published in: The lancet oncology 2020-08, Vol.21 (8), p.1110-1122
• Main Authors: Weiss, Aaron R, Chen, Yen-Lin, Scharschmidt, Thomas J, Chi, Yueh-Yun, Tian, Jing, Black, Jennifer O, Davis, Jessica L, Fanburg-Smith, Julie C, Zambrano, Eduardo, Anderson, James, Arens, Robin, Binitie, Odion, Choy, Edwin, Davis, Justin W, Hayes-Jordan, Andrea, Kao, Simon C, Kayton, Mark L, Kessel, Sandy, Lim, Ruth, Meyer, William H, Million, Lynn, Okuno, Scott H, Ostrenga, Andrew, Parisi, Marguerite T, Pryma, Daniel A, Randall, R Lor, Rosen, Mark A, Schlapkohl, Mary, Shulkin, Barry L, Smith, Ethan A, Sorger, Joel I, Terezakis, Stephanie, Hawkins, Douglas S, Spunt, Sheri L, Wang, Dian
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Adults; Age; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Biopsy; Cancer therapies; Chemoradiotherapy; Chemoradiotherapy - adverse effects; Chemoradiotherapy - methods; Chemotherapy; Chemotherapy, Adjuvant - adverse effects; Chemotherapy, Adjuvant - methods; Child; Child, Preschool; Children; Clinical trials; Collaboration; Consortia; Creatinine; Cytotoxicity; Disease; Doxorubicin; Drug dosages; Ewings sarcoma; FDA approval; Female; Humans; Ifosfamide; Indazoles; Inhibitor drugs; Leukopenia; Liposarcoma; Male; Metastasis; Middle Aged; Neoadjuvant Therapy - adverse effects; Neoadjuvant Therapy - methods; Neutropenia; Oncology; Patients; Pediatrics; Pyrimidines - administration & dosage; Pyrimidines - adverse effects; Radiation therapy; Radiotherapy, Adjuvant; Sarcoma; Sarcoma - drug therapy; Sarcoma - radiotherapy; Soft Tissue Neoplasms - drug therapy; Soft Tissue Neoplasms - radiotherapy; Soft tissue sarcoma; Studies; Sulfonamides - administration & dosage; Sulfonamides - adverse effects; Surgery; Targeted cancer therapy; Toxicity; Tumors; Young Adult
• ISSN: 1470-2045; 1474-5488
• DOI: 10.1016/S1470-2045(20)30325-9

Outcomes for children and adults with advanced soft tissue sarcoma are poor with traditional therapy. We investigated whether the addition of pazopanib to preoperative chemoradiotherapy would improve pathological near complete response rate compared with chemoradiotherapy alone. In this joint Children's Oncology Group and NRG Oncology multicentre, randomised, open-label, phase 2 trial, we enrolled eligible adults (aged ≥18 years) and children (aged between 2 and 16 years) performance status score of at least 70. Patients received ifosfamide (2·5 g/m2 per dose intravenously on days 1–3 with mesna) and doxorubicin (37·5 mg/m2 per dose intravenously on days 1–2) with 45 Gy preoperative radiotherapy, followed by surgical resection at week 13. Patients were randomly assigned (1:1) using a web-based system, in an unmasked manner, to receive oral pazopanib (if patients