期刊
NATURE MEDICINE
卷 26, 期 12, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41591-020-1086-y
关键词
-
资金
- AstraZeneca/MedImmune
- MDACC Immunotherapy Platform, the MD Anderson Physician Scientist Award
- Khalifa Physician Scientist Award
- Andrew Sabin Family Foundation Fellows Award
- Wendy and Leslie Irvin Barnhart Fund
Immune checkpoint therapy is being tested in the neoadjuvant setting for patients with localized urothelial carcinoma(1,2), with one study reporting data in cisplatin-ineligible patients who received anti-PD-L1 monotherapy(2) . 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 disease(3-5). 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.
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