TY - JOUR
T1 - Preoperative ipilimumab plus nivolumab in locoregionally advanced urothelial cancer: the NABUCCO trial
AU - van Dijk, Nick
AU - Gil-Jimenez, Alberto
AU - Silina, Karina
AU - Hendricksen, Kees
AU - Smit, Laura A.
AU - de Feijter, Jeantine M.
AU - van Montfoort, Maurits L.
AU - van Rooijen, Charlotte
AU - Peters, Dennis
AU - Broeks, Annegien
AU - van der Poel, Henk G.
AU - Bruining, Annemarie
AU - Lubeck, Yoni
AU - Sikorska, Karolina
AU - Boellaard, Thierry N.
AU - Kvistborg, Pia
AU - Vis, Daniel J.
AU - Hooijberg, Erik
AU - Schumacher, Ton N.
AU - van den Broek, Maries
AU - Wessels, Lodewyk F. A.
AU - Blank, Christian U.
AU - van Rhijn, Bas W.
AU - van der Heijden, Michiel S.
PY - 2020/12
Y1 - 2020/12
N2 - Preoperative immunotherapy with anti-PD1 plus anti-CTLA4 antibodies has shown remarkable pathological responses in melanoma1 and colorectal cancer2. In NABUCCO (ClinicalTrials.gov: NCT03387761), 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.
AB - Preoperative immunotherapy with anti-PD1 plus anti-CTLA4 antibodies has shown remarkable pathological responses in melanoma1 and colorectal cancer2. In NABUCCO (ClinicalTrials.gov: NCT03387761), 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.
UR - http://www.scopus.com/inward/record.url?scp=85092396181&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41591-020-1085-z
DO - https://doi.org/10.1038/s41591-020-1085-z
M3 - Article
C2 - 33046870
SN - 1078-8956
VL - 26
SP - 1839
EP - 1844
JO - Nature medicine
JF - Nature medicine
IS - 12
ER -