Open-label phase II study of the efficacy of nivolumab for cancer of unknown primary
Open-label phase II study of the efficacy of nivolumab for cancer of unknown primary
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DOI：
10.1016/j.annonc.2021.11.009
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发表时间：
2022-01-20
影响因子：
50.5
通讯作者：
Hayashi, H.
中科院分区：
文献类型：
--
作者：
Tanizaki, J.;Yonemori, K.;Hayashi, H.
背景：原发性不明癌症（CUP）预后不良。鉴于最近批准的几种癌症类型的免疫检查点抑制剂，我们进行了多中心的II期研究，以评估nivolumab的疗效与CUP.Patients和方法的患者：CUP患者谁是以前治疗的至少一个线的全身化疗构成的主要研究人群。既往未接受过治疗的CUP患者也入组进行探索性分析。Nivolumab（240 mg/体）每2周一次给药，最多52个周期。主要终点为既往接受过治疗的患者的客观缓解率，根据RECIST 1.1版进行盲法独立中心评价。结果：共纳入五十六例CUP患者。对于45例既往接受过治疗的患者，客观缓解率为22.2% [95%置信区间（CI），11.2%-37.1%]，中位无进展生存期和总生存期分别为4.0个月（95% CI，1.9-5.8个月）和15.9个月（95% CI，8.4-21.5个月）。在11例既往未接受治疗的患者中也观察到类似的临床获益。nivolumab更好的临床疗效对于具有较高程序性死亡配体1表达水平的肿瘤、具有较高肿瘤突变负荷的肿瘤和微卫星不稳定性高的肿瘤是明显的。相比之下，基于估计的起源组织，肿瘤亚组之间的疗效无明显差异。不良事件与nivolumab的已知安全性特征一致。没有治疗相关的死亡observed.Conclusions：我们的研究结果表明，纳武利尤单抗CUP患者的临床效益，这表明纳武利尤单抗是一个潜在的额外的治疗选择CUP。
Background: Cancer of unknown primary (CUP) has a poor prognosis. Given the recent approval of immune checkpoint inhibitors for several cancer types, we carried out a multicenter phase II study to assess the efficacy of nivolumab for patients with CUP.Patients and methods: Patients with CUP who were previously treated with at least one line of systemic chemotherapy constituted the principal study population. Previously untreated patients with CUP were also enrolled for exploratory analysis. Nivolumab (240 mg/body) was administered every 2 weeks for up to 52 cycles. The primary endpoint was objective response rate in previously treated patients as determined by blinded independent central review according to RECIST version 1.1.Results: Fifty-six patients with CUP were enrolled in the trial. For the 45 previously treated patients, objective response rate was 22.2% [95% confidence interval (CI), 11.2% to 37.1%], with a median progression-free survival and overall survival of 4.0 months (95% CI, 1.9-5.8 months) and 15.9 months (95% CI, 8.4-21.5 months), respectively. Similar clinical benefits were also observed in the 11 previously untreated patients. Better clinical efficacy of nivolumab was apparent for tumors with a higher programmed death-ligand 1 expression level, for those with a higher tumor mutation burden, and for microsatellite instability-high tumors. In contrast, no differences in efficacy were apparent between tumor subgroups based on estimated tissue of origin. Adverse events were consistent with the known safety profile of nivolumab. No treatment-related death was observed.Conclusions: Our results demonstrate a clinical benefit of nivolumab for patients with CUP, suggesting that nivolumab is a potential additional therapeutic option for CUP.