Immune checkpoint therapy is being tested in the neoadjuvant setting for patients with localized urothelial carcinoma1,2, with one study reporting data in cisplatin-ineligible patients who received anti-PD-L1 monotherapy2. The study reported that patients with bulky tumors, a known high-risk feature defined as greater than clinical T2 disease, had fewer responses, with pathological complete response rate of 17%2. Here we report on the first pilot combination neoadjuvant trial ( NCT02812420 ) with anti-PD-L1 (durvalumab) plus anti-CTLA-4 (tremelimumab) in cisplatin-ineligible patients, with all tumors identified as having high-risk features (n = 28). High-risk features were defined by bulky tumors, variant histology, lymphovascular invasion, hydronephrosis and/or high-grade upper tract disease3-5. The primary endpoint was safety and we observed 6 of 28 patients (21%) with grade ≥3 immune-related adverse events, consisting of asymptomatic laboratory abnormalities (n = 4), hepatitis and colitis (n = 2). We also observed pathological complete response of 37.5% and downstaging to pT1 or less in 58% of patients who completed surgery (n = 24). In summary, we provide initial safety, efficacy and biomarker data with neoadjuvant combination anti-PD-L1 plus anti-CTLA-4, which warrants further development for patients with localized urothelial carcinoma, especially cisplatin-ineligible patients with high-risk features who do not currently have an established standard-of-care neoadjuvant treatment.
Nature medicine. 2020 Oct 12 [Epub]
Jianjun Gao, Neema Navai, Omar Alhalabi, Arlene Siefker-Radtke, Matthew T Campbell, Rebecca Slack Tidwell, Charles C Guo, Ashish M Kamat, Surena F Matin, John C Araujo, Amishi Y Shah, Pavlos Msaouel, Paul Corn, Jianbo Wang, John N Papadopoulos, Shalini S Yadav, Jorge M Blando, Fei Duan, Sreyashi Basu, Wenbin Liu, Yu Shen, Yuwei Zhang, Marc Daniel Macaluso, Ying Wang, Jianfeng Chen, Jianhua Zhang, Andrew Futreal, Colin Dinney, James P Allison, Sangeeta Goswami, Padmanee Sharma
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. ., Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., The Immunotherapy Platform, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. .