학술논문
A randomized, non-comparative phase 2 study of neoadjuvant immune-checkpoint blockade in retroperitoneal dedifferentiated liposarcoma and extremity/truncal undifferentiated pleomorphic sarcoma
Document Type
Original Paper
Author
Roland, Christina L.; Nassif Haddad, Elise F.; Keung, Emily Z.; Wang, Wei-Lien; Lazar, Alexander J.; Lin, Heather; Chelvanambi, Manoj; Parra, Edwin R.; Wani, Khalida; Guadagnolo, B. Ashleigh; Bishop, Andrew J.; Burton, Elizabeth M.; Hunt, Kelly K.; Torres, Keila E.; Feig, Barry W.; Scally, Christopher P.; Lewis, Valerae O.; Bird, Justin E.; Ratan, Ravin; Araujo, Dejka; Zarzour, M. Alexandra; Patel, Shreyaskumar; Benjamin, Robert; Conley, Anthony P.; Livingston, J. Andrew; Ravi, Vinod; Tawbi, Hussein A.; Lin, Patrick P.; Moon, Bryan S.; Satcher, Robert L.; Mujtaba, Bilal; Witt, Russell G.; Traweek, Raymond S.; Cope, Brandon; Lazcano, Rossana; Wu, Chia-Chin; Zhou, Xiao; Mohammad, Mohammad M.; Chu, Randy A.; Zhang, Jianhua; Damania, Ashish; Sahasrabhojane, Pranoti; Tate, Taylor; Callahan, Kate; Nguyen, Sa; Ingram, Davis; Morey, Rohini; Crosby, Shadarra; Mathew, Grace; Duncan, Sheila; Lima, Cibelle F.; Blay, Jean-Yves; Fridman, Wolf Herman; Shaw, Kenna; Wistuba, Ignacio; Futreal, Andrew; Ajami, Nadim; Wargo, Jennifer A.; Somaiah, Neeta
Source
Nature Cancer. 5(4):625-641
Subject
Language
English
ISSN
2662-1347
Abstract
Based on the demonstrated clinical activity of immune-checkpoint blockade (ICB) in advanced dedifferentiated liposarcoma (DDLPS) and undifferentiated pleomorphic sarcoma (UPS), we conducted a randomized, non-comparative phase 2 trial (NCT03307616) of neoadjuvant nivolumab or nivolumab/ipilimumab in patients with resectable retroperitoneal DDLPS (n = 17) and extremity/truncal UPS (+ concurrent nivolumab/radiation therapy; n = 10). The primary end point of pathologic response (percent hyalinization) was a median of 8.8% in DDLPS and 89% in UPS. Secondary end points were the changes in immune infiltrate, radiographic response, 12- and 24-month relapse-free survival and overall survival. Lower densities of regulatory T cells before treatment were associated with a major pathologic response (hyalinization > 30%). Tumor infiltration by B cells was increased following neoadjuvant treatment and was associated with overall survival in DDLPS. B cell infiltration was associated with higher densities of regulatory T cells before treatment, which was lost upon ICB treatment. Our data demonstrate that neoadjuvant ICB is associated with complex immune changes within the tumor microenvironment in DDLPS and UPS and that neoadjuvant ICB with concurrent radiotherapy has significant efficacy in UPS.
Roland et al. report the results of a randomized, non-comparative phase 2 trial of neoadjuvant nivolumab or a combination of nivolumab and ipilimumab in patients with resectable retroperitoneal dedifferentiated liposarcoma and extremity/truncal undifferentiated pleomorphic sarcoma.
Roland et al. report the results of a randomized, non-comparative phase 2 trial of neoadjuvant nivolumab or a combination of nivolumab and ipilimumab in patients with resectable retroperitoneal dedifferentiated liposarcoma and extremity/truncal undifferentiated pleomorphic sarcoma.