van Dijk, Nick and Gil-Jimenez, Alberto and Silina, Karina and Hendricksen, Kees and Smit, Laura A. and de Feijter, Jeantine M. and van Montfoort, Maurits L. and van Rooijen, Charlotte and Peters, Dennis and Broeks, Annegien and van der Poel, Henk G. and Bruining, Annemarie and Lubeck, Yoni and Sikorska, Karolina and Boellaard, Thierry N. and Kvistborg, Pia and Vis, Daniel J. and Hooijberg, Erik and Schumacher, Ton N. and van den Broek, Maries and Wessels, Lodewyk F. A. and Blank, Christian U. and van Rhijn, Bas W. and van der Heijden, Michiel S. (2020) Preoperative ipilimumab plus nivolumab in locoregionally advanced urothelial cancer: the NABUCCO trial. NATURE MEDICINE, 26 (12). ISSN 1078-8956, 1546-170X
Full text not available from this repository. (Request a copy)Abstract
Preoperative immunotherapy with anti-PD1 plus anti-CTLA4 antibodies has shown remarkable pathological responses in melanoma(1)and colorectal cancer(2). In NABUCCO (ClinicalTrials.gov:), a single-arm feasibility trial, 24 patients with stage III urothelial cancer (UC) received two doses of ipilimumab and two doses of nivolumab, followed by resection. The primary endpoint was feasibility to resect within 12 weeks from treatment start. All patients were evaluable for the study endpoints and underwent resection, 23 (96%) within 12 weeks. Grade 3-4 immune-related adverse events occurred in 55% of patients and in 41% of patients when excluding clinically insignificant laboratory abnormalities. Eleven patients (46%) had a pathological complete response (pCR), meeting the secondary efficacy endpoint. Fourteen patients (58%) had no remaining invasive disease (pCR or pTisN0/pTaN0). In contrast to studies with anti-PD1/PD-L1 monotherapy, complete response to ipilimumab plus nivolumab was independent of baseline CD8(+) presence or T-effector signatures. Induction of tertiary lymphoid structures upon treatment was observed in responding patients. Our data indicate that combined CTLA-4 plus PD-1 blockade might provide an effective preoperative treatment strategy in locoregionally advanced UC, irrespective of pre-existing CD8(+)T cell activity.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TERTIARY LYMPHOID STRUCTURES; CISPLATIN-INELIGIBLE PATIENTS; INVASIVE BLADDER-CANCER; SINGLE-ARM; NEOADJUVANT CHEMOTHERAPY; B-CELLS; MULTICENTER; BLOCKADE; CARCINOMA; IMMUNOTHERAPY; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Urologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Mar 2021 06:45 |
| Last Modified: | 09 Mar 2021 06:45 |
| URI: | https://pred.uni-regensburg.de/id/eprint/43573 |
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