一项关于五种肽联合奥沙利铂化疗作为晚期结直肠癌一线治疗的II期研究（FXV研究）。
A phase ΙI study of five peptides combination with oxaliplatin-based chemotherapy as a first-line therapy for advanced colorectal cancer (FXV study).
作者信息
Hazama Shoichi, Nakamura Yusuke, Tanaka Hiroaki, Hirakawa Kosei, Tahara Ko, Shimizu Ryoichi, Ozasa Hiroaki, Etoh Ryuichi, Sugiura Fumiaki, Okuno Kiyotaka, Furuya Takumi, Nishimura Taku, Sakata Koichiro, Yoshimatsu Kazuhiko, Takenouchi Hiroko, Tsunedomi Ryouichi, Inoue Yuka, Kanekiyo Shinsuke, Shindo Yoshitaro, Suzuki Nobuaki, Yoshino Shigefumi, Shinozaki Hirokazu, Kamiya Akira, Furukawa Hiroyuki, Yamanaka Takeharu, Fujita Tomonobu, Kawakami Yutaka, Oka Masaaki
机构信息
Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Ube, Japan.
出版信息
J Transl Med. 2014 Apr 30;12:108. doi: 10.1186/1479-5876-12-108.
BACKGROUND
We previously conducted a phase I trial for advanced colorectal cancer (CRC) using five HLA-A*2402-restricted peptides, three derived from oncoantigens and two from vascular endothelial growth factor (VEGF) receptors, and confirmed safety and immunological responses. To evaluate clinical benefits of cancer vaccination treatment, we conducted a phase II trial using the same peptides in combination with oxaliplatin-based chemotherapy as a first-line therapy.
METHODS
The primary objective of the study was the response rates (RR). Progression free survival (PFS), overall survival (OS), and immunological parameters were evaluated as secondary objective. The planned sample size was more than 40 patients for both HLA2402-matched and -unmatched groups. All patients received a cocktail of five peptides (3 mg each) mixed with 1.5 ml of IFA which was subcutaneously administered weekly for the first 12 weeks followed by biweekly administration. Presence or absence of the HLA-A*2402 genotype were used for classification of patients into two groups.
RESULTS
Between February 2009 and November 2012, ninety-six chemotherapy naïve CRC patients were enrolled under the masking of their HLA-A status. Ninety-three patients received mFOLFOX6 and three received XELOX. Bevacizumab was added in five patients. RR was 62.0% and 60.9% in the HLA-A2402-matched and -unmatched groups, respectively (p=0.910). The median OS was 20.7 months in the HLA-A2402-matched group and 24.0 months in the unmatched group (log-rank, p=0.489). In subgroup with a neutrophil/lymphocyte ratio (NLR) of <3.0, patients in the HLA-matched group did not survive significantly longer than those in the unmatched group (log-rank, p=0.289) but showed a delayed response.
CONCLUSIONS
Although no significance was observed for planned statistical efficacy endpoints, a delayed response was observed in subgroup with a NLR of <3.0. Biomarkers such as NLR might be useful for selecting patients with a better treatment outcome by the vaccination.
TRIAL REGISTRATION
Trial registration: UMIN000001791.
背景
我们之前针对晚期结直肠癌（CRC）开展了一项I期试验，使用了五种HLA - A*2402限制性肽段，其中三种源自癌抗原，两种源自血管内皮生长因子（VEGF）受体，并证实了其安全性和免疫反应。为了评估癌症疫苗治疗的临床益处，我们开展了一项II期试验，使用相同的肽段联合基于奥沙利铂的化疗作为一线治疗。
方法
该研究的主要目标是缓解率（RR）。无进展生存期（PFS）、总生存期（OS）和免疫参数作为次要目标进行评估。HLA2402匹配组和不匹配组的计划样本量均超过40例患者。所有患者接受五种肽段（各3 mg）与1.5 ml不完全弗氏佐剂（IFA）的混合制剂，在前12周每周皮下注射一次，之后每两周注射一次。根据是否存在HLA - A*2402基因型将患者分为两组。
结果
在2009年2月至2012年11月期间，96例未经化疗的CRC患者在其HLA - A状态被掩盖的情况下入组。93例患者接受了mFOLFOX6方案，3例接受了XELOX方案。5例患者加用了贝伐单抗。HLA - A2402匹配组和不匹配组的RR分别为62.0%和60.9%（p = 0.910）。HLA - A2402匹配组的中位OS为20.7个月，不匹配组为24.0个月（对数秩检验，p = 0.489）。在中性粒细胞/淋巴细胞比值（NLR）<3.0的亚组中，HLA匹配组患者的生存期并不显著长于不匹配组患者（对数秩检验，p = 0.289），但缓解出现延迟。
结论
尽管在计划的统计学疗效终点方面未观察到显著性差异，但在NLR<3.0的亚组中观察到了缓解延迟。诸如NLR等生物标志物可能有助于通过疫苗接种选择治疗效果更好的患者。
试验注册
试验注册号：UMIN000001791。
Zotero 插件