工程化益生菌用于肿瘤靶向联合化学免疫治疗
Engineered probiotics for tumor-targeted combination chemoimmunotherapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
帕博利珠单抗在晚期原发灶不明癌（CUP）患者中的疗效：一项 2 期非随机临床试验
英文原题：Efficacy of pembrolizumab in patients with advanced cancer of unknown primary (CUP): a phase 2 non-randomized clinical trial.
查看英文原题
Efficacy of pembrolizumab in patients with advanced cancer of unknown primary (CUP): a phase 2 non-randomized clinical trial.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
研究概要
帕博利珠单抗在 CUP 患者中显示出令人鼓舞的疗效，且安全性可接受。
研究思路结论见上方概要
背景
原发灶不明癌（CUP）是一种侵袭性罕见恶性肿瘤，治疗选择有限。关于免疫检查点抑制剂在CUP中临床活性的数据尚缺乏。因此，我们评估了pembrolizumab（一种程序性细胞死亡-1抑制剂）在CUP患者中的疗效。
方法
该研究设计为一项2期篮式试验，针对包括CUP在内的独立罕见肿瘤队列。符合条件的患者为既往系统治疗进展、体能状态0/1、根据实体瘤疗效评价标准（RECIST V.1.1）具有可测量病灶的成人CUP患者。患者接受pembrolizumab（200 mg）静脉注射，每21天一次。2016年8月至2020年6月期间共入组并治疗29例患者。主要终点为根据免疫相关RECIST评估的27周无进展率（NPR-27）。预先设定的关键次要终点为确认的客观缓解率（ORR）、安全性、缓解持续时间（DoR）、无进展生存期（PFS）和总生存期（OS）。对治疗前活检组织进行应答生物标志物检测（程序性细胞死亡配体-1（PD-L1）表达和TIL（肿瘤浸润淋巴细胞）（TILs））。
结果
在29例入组患者中，25例符合条件且可评估，其中14例（56%）为低分化癌。患者入组前接受过中位两线治疗。中位随访时间为27.3个月。7例患者（28.0%（95% CI：12.1至49.4））观察到NPR-27。ORR为20.0%（95% CI：6.8至40.7），5例患者达到免疫相关部分缓解，中位DoR为14.7个月（95% CI：9.8至19.6）。中位PFS和OS分别为4.1个月（95% CI：3.1至5.1）和11.3个月（95% CI：5.5至17.1）。任何级别和治疗相关3级不良事件分别见于19例（76%）和4例（16%）患者。1例（4%）患者发生3级免疫相关急性肾损伤，需要终止治疗。PD-L1和TILs均与NPR-27无关。PD-L1阳性染色（44.4% vs 6.3%；p=0.040）和TIL密集浸润（44.4% vs 6.3%；p=0.040）均与缓解相关。
展开英文摘要原文
BACKGROUND
Cancer of unknown primary (CUP) is an aggressive rare malignancy with limited treatment options. Data regarding clinical activity of immune checkpoint inhibitors in CUP is lacking. Therefore, we evaluated the efficacy of pembrolizumab, a programmed cell death-1 inhibitor, in patients with CUP.
METHODS
The study was designed as a phase 2 basket trial for independent rare tumor cohorts including CUP. Adult patients with CUP who had progressed on previous systemic therapy, performance status 0/1 and measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST V.1.1) were eligible. Patients received pembrolizumab (200 mg) intravenously every 21 days. Twenty-nine patients were enrolled and treated between August 2016 and June 2020. The primary endpoint was non-progression rate (NPR) at 27 weeks (NPR-27) per immune-related RECIST. Key prespecified secondary endpoints were confirmed objective response rate (ORR), safety, duration of response (DoR), progression-free survival (PFS) and overall survival (OS). Pretreatment biopsies were examined for biomarkers of response (programmed cell death ligand-1 (PD-L1) expression and tumor infiltrating lymphocytes (TILs)).
RESULTS
Among 25 (of 29 enrolled) eligible and evaluable patients, 14 (56%) had poorly differentiated carcinoma. Patients received a median of two lines of therapy prior to enrollment. Median follow-up was 27.3 months. NPR-27 was observed in seven patients (28.0% (95% CI: 12.1 to 49.4)). ORR was 20.0% (95% CI: 6.8 to 40.7) with five patients achieving immune-related partial response with median DoR of 14.7 months (95% CI: 9.8 to 19.6). Median PFS and OS were 4.1 (95% CI: 3.1 to 5.1) and 11.3 (95% CI: 5.5 to 17.1) months, respectively. Treatment-related adverse events of any and grade 3 were seen in 19 (76%) and 4 (16%) patients, respectively. One (4%) patient had grade 3 immune-related acute kidney injury requiring treatment discontinuation. Neither PD-L1 nor TILs were associated with NPR-27. Both positive PD-L1 staining (44.4% vs 6.3%; p=0.040) and intense TIL infiltration (44.4% vs 6.3%; p=0.040) were associated with response.
CONCLUSION
Pembrolizumab showed encouraging efficacy in patients with CUP with acceptable safety profile. TRIAL REGISTRATION NUMBER: NCT02721732.
论文信息
- 作者
- Raghav KP、Stephen B、Karp DD、Piha-Paul SA、Hong DS、Jain D、Chudy Onwugaje DO、Abonofal A
- 第一作者单位
- Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA anaing@mdanderson.org KPRaghav@mdanderson.org.United States
- 通讯作者单位
- Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA anaing@mdanderson.org KPRaghav@mdanderson.org.United States
- 文献类型
- II 期临床试验 · 美国 NIH 资助研究 · 非美国政府资助研究
- 期刊
- Journal for immunotherapy of cancer2022 May
- 原文标识
- PubMed 35618285 · DOI 10.1136/jitc-2022-004822
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