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Top Line: Multiple studies of neoadjuvant therapy for soft tissue sarcoma (STS) have shown an association between pathologic complete response and survival outcomes.
The Study: Neoadjuvant radiation is frequently used for STS, and another option is to add doxorubicin-based neoadjuvant chemotherapy. ARST1321 is (surprisingly?) the first collaborative study between a pediatric and adult oncology cooperative group. It arose when investigators from both COG and NRG independently proposed adding pazopanib to neoadjuvant radiation and chemo for locally advanced STS. Why pazopanib? It’s a multi-tyrosine kinase inhibitor that targets both VEGF and PDGF among a number of other receptors, and it has activity in metastatic STS. So this trial enrolled 81 patients of all ages with tumors >5 cm of intermediate or high grade receiving neoadjuvant radiation to 45 Gy concurrent to ifosfamide and doxorubicin +/- pazopanib. The primary outcome was the rate of 90+% pathologic response (aka “near-complete” response #trendalert). This interim analysis of 42 patients suggests pazopanib nearly tripled this "near-complete" response rate from 22 → 58%. The median extent of response was 95% with pazopanib versus 50% without. Only time will tell if this translates to improved survival outcomes.
TBL: Adding pazopanib to neoadjuvant chemoradiation appears to improve path response rate of high-risk soft tissue sarcoma in patients of all ages. | Weiss, Lancet Oncol 2020