Neoadjuvant combination PD-L1 plus CTLA-4 blockade in patients with cisplatin-ineligible operable urothelial carcinoma
Immune checkpoint therapy (ICT) is being tested in the neoadjuvant setting for patients with localized urothelial carcinoma (UC), with one study reporting data in cisplatin-ineligible patients who received anti PD-L1 monotherapy. The study reported that patients with bulky tumors, a known high-risk feature defined as greater than clinical T2 disease, had fewer responses, with pathologic complete response (pCR) rate of 17%. 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). 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 pCR 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 UC, especially cisplatin-ineligible patients with high-risk features who do not currently have an established standard-of-care neoadjuvant treatment. Publication: Gao et al. Neoadjuvant PD-L1 plus CTLA-4 blockade in patients with cisplatin-ineligible operable high-risk urothelial carcinoma. Nature Medicine volume 26, pages1845–1851(2020)
- Type: Other
- Archiver: European Genome-Phenome Archive (EGA)
Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data
Dataset ID | Description | Technology | Samples |
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EGAD00001005712 | Illumina HiSeq 2000 | 46 | |
EGAD00010001852 | Nanostring expression immunology panel | 34 |
Publications | Citations |
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Neoadjuvant PD-L1 plus CTLA-4 blockade in patients with cisplatin-ineligible operable high-risk urothelial carcinoma.
Nat Med 26: 2020 1845-1851 |
116 |