Paclitaxel liposome for injection (Lipusu) plus cisplatin versus gemcitabine plus cisplatin in the first-line treatment of locally advanced or metastatic lung squamous cell carcinoma: A multicenter, randomized, open-label, parallel controlled clinical study

Cancer Communications

article

Jie Zhang¹  Yueyin Pan³  Qin Shi⁴  Guojun Zhang⁵  Liyan Jiang⁶  Xiaorong Dong⁷  Kangsheng Gu⁸  Huijuan Wang⁹  Xiaochun Zhang^1,10  Nong Yang^1,11  Yuping Li^1,12  Jianping Xiong^1,13  Tienan Yi^1,14  Min Peng^1,15  Yong Song^1,16  Yun Fan^1,17  Jiuwei Cui^1,18  Gongyan Chen^1,19  Wei Tan^2,20  Aimin Zang^2,21  Qisen Guo^2,22  Guangqiang Zhao^2,23  Ziping Wang^2,24  Jianxing He^2,25  Wenxiu Yao^2,26  Xiaohong Wu^2,27  Kai Chen^2,28  Xiaohua Hu^2,29  Chunhong Hu^3,30  Lu Yue^3,31  Da Jiang^3,32  Guangfa Wang^3,33  Junfeng Liu^3,34  Guohua Yu^3,35  Junling Li^3,36  Jianling Bai^3,37  Wenmin Xie^3,38  Weihong Zhao^3,38  Lihong Wu^3,39  Caicun Zhou¹ 

[1] Department of Medical Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, Tongji University School of Medicine;These authors contributed equally to this work.;Department of Chemotherapy, Anhui Provincial Hospital;Department of Oncology, Fuzhou Pulmonary Hospital of Fujian;Department of Respiratory Medicine, the First Affiliated Hospital of Zhengzhou University;Department of Respiration, Shanghai Chest Hospital, Shanghai Jiao Tong University;Cancer Center, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology;Department of Medical Oncology, the First Affiliated Hospital of Anhui Medical University;Department of Respiration, Henan Cancer Hospital;Department of Medical Oncology, the Affiliated Hospital of Qingdao University;Department of Medical Oncology, Hunan Cancer Hospital;Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Wenzhou Medical College;Department of Medical Oncology, the First Affiliated Hospital of Nanchang University;Department of Medical Oncology, Xiang Yang Central Hospital;Department of Medical Oncology, Renmin Hospital of Wuhan University;Department of Respiration, General Hospital of Eastern Theater Command of Chinese People's Liberation Army;Department of Medical Oncology, Zhejiang Cancer Hospital;Cancer Center, the First Bethune Hospital of Jilin University;Department of Medical Oncology, Harbin Medical University Cancer Hospital;Department of Respiratory Medicine, Weifang People's Hospital;Department of Medical Oncology, Affiliated Hospital of Hebei University;Department of Internal Medicine, Shandong Cancer Hospital & Institute;Department of Thoracic Surgery,  the Third Affiliated Hospital of Kunming Medical University;Department of Medical Oncology, Beijing Cancer Hospital;Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University;Department of Chemotherapy, Sichuan Cancer Hospital & Institute;Department of Medical Oncology, the Fourth People's Hospital of Wuxi;Department of Medical Oncology, the First Affiliated Hospital of Soochow University;Department of Medical Oncology, the First Affiliated Hospital of Guangxi Medical University;Department of Medical Oncology, the Second Xiangya Hospital of Central South University;Department of Medical Oncology, Qingdao Municipal Hospital;Department of Medical Oncology, the 4th Hospital of Hebei Medical University;Department of Respiratory Medicine, Peking University First Hospital;Department of Thoracic Surgery, the 4th Hospital of Hebei Medical University;Department of Medical Oncology, Weifang People's Hospital;Cancer Hospital Chinese Academy of Medical Sciences;Department of Biostatistics, School of Public Health, Nanjing Medical University;Nanjing Luye Pharmaceutical Co., Ltd;Genecast Biotechnology Co., Ltd

关键词: chemotherapy;    cisplatin;    clinical trial;    gemcitabine;    liposomal paclitaxel (Lipusu);    locally advanced;    lung squamous cell carcinoma;    metastatic;    multicenter;    plasma cytokines;   

DOI  :  10.1002/cac2.12225

学科分类：社会科学、人文和艺术（综合）

来源: Springer

【 摘 要 】

Background Lipusu is the first commercialized liposomal formulation of paclitaxel and has demonstrated promising efficacy against locally advanced lung squamous cell carcinoma (LSCC) in a small-scale study. Here, we conducted a multicenter, randomized, phase 3 study to compare the efficacy and safety of cisplatin plus Lipusu (LP) versus cisplatin plus gemcitabine (GP) as first-line treatment in locally advanced or metastatic LSCC. Methods Patients enrolled were aged between 18 to 75 years, had locally advanced (clinical stage IIIB, ineligible for concurrent chemoradiation or surgery) or metastatic (Stage IV) LSCC, had no previous systemic chemotherapy and at least one measurable lesion as per the Response Evaluation Criteria in Solid Tumors (version 1.1) before administration of the trial drug. The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety profiles. To explore the possible predictive value of plasma cytokines for LP treatment, plasma samples were collected from the LP group at baseline and first efficacy evaluation time and were then subjected to analysis by 45-Plex ProcartaPlex Panel 1 to detect the presence of 45 cytokines using the Luminex xMAP technology. The correlation between treatment outcomes and dynamic changes in the levels of cytokines were evaluated in preliminary analyses. Results The median duration of follow-up was 15.4 months. 237 patients in the LP group and 253 patients in the GP group were included in the per protocol set (PPS). In the PPS, the median PFS was 5.2 months versus 5.5 months in the LP and GP group (hazard ratio [HR]: 1.03, P = 0.742) respectively. The median OS was 14.6 months versus 12.5 months in the LP and GP group (HR: 0.83, P = 0.215). The ORR (41.8% versus 45.9%, P = 0.412) and DCR (90.3% versus 88.1%, P = 0.443) were also similar between the LP and GP group. A significantly lower proportion of patients in the LP group experienced adverse events (AEs) leading to treatment interruptions (10.9% versus 26.4%, P < 0.001) or treatment termination (14.3% versus 23.1%, P = 0.011). The analysis of cytokine levels in the LP group showed that low baseline levels of 27 cytokines were associated with an increased ORR, and 15 cytokines were associated with improved PFS, with 14 cytokines, including TNF-α, IFN-γ, IL-6, and IL-8, demonstrating an overlapping trend. Conclusion The LP regimen demonstrated similar PFS, OS, ORR and DCR as the GP regimen for patients with locally advanced or metastatic LSCC but had more favorable toxicity profiles. The study also identified a spectrum of different cytokines that could be potentially associated with the clinical benefit in patients who received the LP regimen.

【 授权许可】

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