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Neoadjuvant PD-L1 plus CTLA-4 blockade in patients with cisplatin-ineligible operable high-risk urothelial carcinoma

Researchers at the University of Texas MD Anderson Cancer Center report on a pilot clinical trial of 28 patients with high-risk urothelial carcinoma treated with anti-PD-L1 (durvalumab) and anti-CTLA-4 (tremelimumab) prior to surgery. Patients in this trial were not able to receive the traditional cisplatin chemotherapy, as is the case for about half of patients with muscle-invasive urothelial carcinoma. The study reports a pathological complete response of 37.5% and downstaging in 58% of patients. HALO image analysis software was used for quantification of single stain immunohistochemistry (CD8, CD4, CD20, FoxP3, and CD21) on pre-treatment tumor samples from patients. The authors conclude that the neoadjuvant treatment combination of durvalumab and tremelimumab warrant further study in patients who are ineligible to receive cisplatin.

Gao J, Navai N, Alhalabi O, Siefker-Radtke A, Campbell MT, Tidwell RS, Guo CC, Kamat AM, Matin SF, Araujo CJ, Shah AY, Msaouel P, Corn P, Wang J, Papadopoulos JN, Yadav SS, Blando JM, Duan F, Basu S, Liu W, Shen Y, Macaluso MD, Wang Y, Chen J, Zhang J, Futreal A, Dinney C, Allison JP, Goswami S, Sharma P

Nature Medicine volume | First published 12 October 2020 | DOI https://doi.org/10.1038/s41591-020-1086-y