Nishio Makoto, Hida Toyoaki, Atagi Shinji, Sakai Hiroshi, Nakagawa Kazuhiko, Takahashi Toshiaki, Nogami Naoyuki, Saka Hideo, Takenoyama Mitsuhiro, Maemondo Makoto, Ohe Yuichiro, Nokihara Hiroshi, Hirashima Tomonori, Tanaka Hiroshi, Fujita Shiro, Takeda Koji, Goto Koichi, Satouchi Miyako, Isobe Hiroshi, Minato Koichi, Sumiyoshi Naoki, Tamura Tomohide
Department of Thoracic Medical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
Department of Thoracic Oncology, Aichi Cancer Center Hospital, Aichi, Japan.
ESMO Open. 2017 Mar 7;1(4):e000108. doi: 10.1136/esmoopen-2016-000108. eCollection 2016.
Nivolumab is a fully human IgG4 programmed cell death 1 immune checkpoint inhibitor monoclonal antibody approved for the treatment of non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the safety and efficacy of nivolumab in Japanese patients with advanced or recurrent non-squamous NSCLC.
In this multicentre phase II study, patients with advanced or recurrent non-squamous NSCLC, which had progressed after platinum-containing chemotherapy, were treated with nivolumab 3 mg/kg, intravenously every 2 weeks until progressive disease or unacceptable toxicity was observed. The primary end point was independent radiology review committee (IRC) assessed overall response rate (ORR) and the secondary endpoints included ORR (investigator assessed), progression-free survival (PFS), overall survival (OS), duration of response, time to response, best overall response, and safety.
76 patients were enrolled across 19 sites in Japan. The ORR (IRC assessed) was 22.4% (95% CI 14.5% to 32.9%). The median PFS and OS were 2.8 months (95% CI 1.4 to 3.4) and 17.1 months (95% CI 13.3 to 23.0), respectively. The OS rate at 1 year was 68.0% (95% CI 56.2% to 77.3%). Current/former smokers were more responsive to treatment than non-smokers (ORR 29.1% vs 4.8%). Patients with epidermal growth factor receptor (EGFR) mutation wild type/unknown showed higher ORR compared with EGFR mutation-positive patients (ORR 28.6% vs 5.0%) and programmed cell death ligand-1 (PD-L1) expression was likely associated with higher ORR, longer PFS and OS. Treatment-related adverse events of grade 3 or higher were reported in 17 patients; these events resolved or were resolving with appropriate treatment including steroid therapy or discontinuation of nivolumab.
Nivolumab was well tolerated and showed clinical efficacy in Japanese patients with non-squamous NSCLC progressed after platinum-containing chemotherapy, especially in those with a history of smoking, wild type/unknown EGFR mutation status or positive PD-L1 expression.
JapicCTI-132073.
纳武利尤单抗是一种全人源IgG4程序性细胞死亡蛋白1免疫检查点抑制剂单克隆抗体，已被批准用于治疗非小细胞肺癌（NSCLC）。本研究的目的是评估纳武利尤单抗在日本晚期或复发性非鳞状NSCLC患者中的安全性和疗效。
在这项多中心II期研究中，对含铂化疗后病情进展的晚期或复发性非鳞状NSCLC患者，采用纳武利尤单抗3mg/kg静脉注射，每2周一次，直至观察到疾病进展或出现不可接受的毒性。主要终点是独立放射学审查委员会（IRC）评估的总缓解率（ORR），次要终点包括ORR（研究者评估）、无进展生存期（PFS）、总生存期（OS）、缓解持续时间、缓解时间、最佳总体缓解以及安全性。
日本19个地点共纳入76例患者。IRC评估的ORR为22.4%（95%CI 14.5%至32.9%）。中位PFS和OS分别为2.8个月（95%CI 1.4至3.4）和17.1个月（95%CI 13.3至23.0）。1年时的OS率为68.0%（95%CI 56.2%至77.3%）。当前/既往吸烟者对治疗的反应比不吸烟者更好（ORR 29.1%对4.8%）。表皮生长因子受体（EGFR）突变野生型/未知的患者与EGFR突变阳性患者相比，ORR更高（ORR 28.6%对5.0%），程序性细胞死亡配体-1（PD-L1）表达可能与更高的ORR、更长的PFS和OS相关。17例患者报告了3级或更高等级的治疗相关不良事件；这些事件通过包括类固醇治疗或停用纳武利尤单抗在内的适当治疗得以缓解或正在缓解。
纳武利尤单抗耐受性良好，在含铂化疗后病情进展的日本非鳞状NSCLC患者中显示出临床疗效，尤其是在有吸烟史、EGFR突变状态为野生型/未知或PD-L1表达阳性的患者中。
JapicCTI-132073。
