Sharma Padmanee, Callahan Margaret K, Bono Petri, Kim Joseph, Spiliopoulou Pavlina, Calvo Emiliano, Pillai Rathi N, Ott Patrick A, de Braud Filippo, Morse Michael, Le Dung T, Jaeger Dirk, Chan Emily, Harbison Chris, Lin Chen-Sheng, Tschaika Marina, Azrilevich Alex, Rosenberg Jonathan E
Department of Genitourinary Medical Oncology, Department of Immunology, MD Anderson Cancer Center, University of Texas, Houston, TX, USA.
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Lancet Oncol. 2016 Nov;17(11):1590-1598. doi: 10.1016/S1470-2045(16)30496-X. Epub 2016 Oct 9.
Few effective treatments exist for patients with advanced urothelial carcinoma that has progressed after platinum-based chemotherapy. We assessed the activity and safety of nivolumab in patients with locally advanced or metastatic urothelial carcinoma whose disease progressed after previous platinum-based chemotherapy.
In this phase 1/2, multicentre, open-label study, we enrolled patients (age ≥18 years) with urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra at 16 sites in Finland, Germany, Spain, the UK, and the USA. Patients were not selected by PD-L1 expression, but tumour PD-L1 membrane expression was assessed retrospectively. Patients received nivolumab 3 mg/kg intravenously every 2 weeks until disease progression or treatment discontinuation because of unacceptable toxicity or other protocol-defined reasons, whichever occurred later. The primary endpoint was objective response by investigator assessment. All patients who received at least one dose of the study drug were included in the analyses. We report an interim analysis of this ongoing trial. CheckMate 032 is registered with ClinicalTrials.gov, NCT01928394.
Between June 5, 2014, and April 24, 2015, 86 patients with metastatic urothelial carcinoma were enrolled in the nivolumab monotherapy group and 78 received at least one dose of treatment. At data cutoff (March 24, 2016), the minimum follow-up was 9 months (median 15·2 months, IQR 12·9-16·8). A confirmed investigator-assessed objective response was achieved in 19 (24·4%, 95% CI 15·3-35·4) of 78 patients. Grade 3-4 treatment-related adverse events occurred in 17 (22%) of 78 patients; the most common were elevated lipase (four [5%]), elevated amylase (three [4%]), and fatigue, maculopapular rash, dyspnoea, decreased lymphocyte count, and decreased neutrophil count (two [3%] each). Serious adverse events were reported in 36 (46%) of 78 patients and eight (10%) had a serious adverse event judged to be treatment related. Two (3%) of 78 patients discontinued because of treatment-related adverse events (grade 4 pneumonitis and grade 4 thrombocytopenia) and subsequently died.
Nivolumab monotherapy was associated with a substantial and durable clinical response and a manageable safety profile in previously treated patients with locally advanced or metastatic urothelial carcinoma. These data support further investigation of nivolumab monotherapy in advanced urothelial carcinoma.
Bristol-Myers Squibb.
对于铂类化疗后病情进展的晚期尿路上皮癌患者，有效的治疗方法很少。我们评估了纳武单抗在先前铂类化疗后病情进展的局部晚期或转移性尿路上皮癌患者中的活性和安全性。
在这项1/2期、多中心、开放标签研究中，我们在芬兰、德国、西班牙、英国和美国的16个地点招募了年龄≥18岁的肾盂、输尿管、膀胱或尿道尿路上皮癌患者。患者未根据PD-L1表达进行选择，但对肿瘤PD-L1膜表达进行了回顾性评估。患者每2周静脉注射3mg/kg纳武单抗，直至疾病进展或因不可接受的毒性或其他方案定义的原因停药，以先发生者为准。主要终点是研究者评估的客观缓解。所有接受至少一剂研究药物的患者均纳入分析。我们报告了这项正在进行的试验的中期分析。CheckMate 032已在ClinicalTrials.gov注册，注册号为NCT01928394。
2014年6月5日至2015年4月24日，86例转移性尿路上皮癌患者入组纳武单抗单药治疗组，78例接受了至少一剂治疗。在数据截止时（2016年3月24日），最短随访时间为9个月（中位数15.2个月，四分位间距12.9 - 16.8个月）。78例患者中有19例（24.4%，95%CI 15.3 - 35.4%）经研究者确认达到客观缓解。78例患者中有17例（22%）发生3 - 4级治疗相关不良事件；最常见的是脂肪酶升高（4例[5%]）、淀粉酶升高（3例[
