小柯机器人

荷兰癌症研究所Michiel S. van der Heijden研究组取得最新进展。他们报告了局部晚期尿路上皮癌的术前伊利木单抗加尼莫单抗治疗试验。相关论文于2020年10月12日发表于国际顶尖学术期刊《自然-医学》。

抗PD1和抗CTLA4抗体的术前免疫疗法在黑色素瘤和大肠癌中显示出显著的病理反应。在NABUCCO（ClinicalTrials.gov：NCT03387761）的单臂可行性试验中，有24例III期尿路上皮癌（UC）患者接受了两剂伊利木单抗和两剂尼莫单抗治疗，然后切除。主要终点是在治疗开始后12周内切除的可行性。所有患者均可评估研究终点，并在12周内接受了切除手术，其中23例（96％）。当排除临床上可忽略的实验室异常时，35％至4级免疫相关不良事件发生在55％的患者和41％的患者中。

11名患者（46％）具有病理完全缓解（pCR），达到了次要疗效终点。 14名患者（58％）没有剩余的浸润性疾病（pCR或pTisN0 / pTaN0）。与抗PD1 / PD-L1单一疗法的研究相比，对伊利木单抗加尼莫单抗的完全反应与基线CD8 +存在或T效应子信号无关。在应答的患者中观察到三级淋巴样结构在治疗后的诱导。

他们的数据表明，CTLA-4加PD-1的联合阻滞可能会在局部晚期UC中提供有效的术前治疗策略，而与先前存在的CD8 + T细胞活性无关。

附：英文原文

Title: Preoperative ipilimumab plus nivolumab in locoregionally advanced urothelial cancer: the NABUCCO trial

Author: Nick van Dijk, Alberto Gil-Jimenez, Karina Silina, Kees Hendricksen, Laura A. Smit, Jeantine M. de Feijter, Maurits L. van Montfoort, Charlotte van Rooijen, Dennis Peters, Annegien Broeks, Henk G. van der Poel, Annemarie Bruining, Yoni Lubeck, Karolina Sikorska, Thierry N. Boellaard, Pia Kvistborg, Daniel J. Vis, Erik Hooijberg, Ton N. Schumacher, Maries van den Broek, Lodewyk F. A. Wessels, Christian U. Blank, Bas W. van Rhijn, Michiel S. van der Heijden

Issue&Volume: 2020-10-12

Abstract: 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.

DOI: 10.1038/s41591-020-1085-z

Source: https://www.nature.com/articles/s41591-020-1085-z

Nature Medicine：《自然—医学》，创刊于1995年。隶属于施普林格·自然出版集团，最新IF：87.241
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