Omori Miwako, Okuma Yusuke, Hakozaki Taiki, Hosomi Yukio
Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo 113-867, Japan.
Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo 113-8603, Japan.
Mol Clin Oncol. 2019 Jan;10(1):137-143. doi: 10.3892/mco.2018.1765. Epub 2018 Nov 13.
There are a number of suggested predictive factors of nivolumab for non-small cell lung cancer (NSCLC), however, there is not enough evidence to determine a single factor that can predict the efficacy of nivolumab. As the progress of biomarkers for cancer treatment is improving, it has been speculated that certain clinical factors serve an important role when predicting the outcome of chemotherapy. A total of 67 patients treated with nivolumab for NSCLC from 2016-2017 were prospectively investigated. Age, sex, the Eastern Cooperative Oncology Group Performance Status, histology, epidermal growth factor receptor (EGFR) mutation, history of chemotherapy, smoking status, use of statins, use of fibrates, use of dipeptidyl peptidase-4 (DPP-4) inhibitors, and use of metformin were examined as clinical factors. Statistical analyses were performed using the Kaplan-Meier method and Cox regression adjusted for risk factors and the tumor response of 67 patients was assessed. The patients had a median age of 67 years (range, 36-87 years), and 46 males and 21 females were enrolled; performance status 0/1 was 59. Cases were categorized as adenocarcinoma (n=41), squamous cell carcinoma (n=17) and other (n=9). A total of 13 patients (19.4%) had EGFR mutations. These clinical factors were not statistically significant in overall survival (OS). Clinical laboratory findings, complications and use of medical agents including antidiabetes mellitus or lipidemia were also analyzed. Statins exhibited statistical significance for response (P=0.02). Time-to-treatment failure (TTF) in statin-use group was not reached [95% confidence interval (CI): 1.9-not reached] and was 4.0 months (95% CI: 2.0-5.4) in the non-statin group (P=0.039). The median OS in statin-use group was not reached (95% CI: 8.7-not reached) and was 16.5 months (95% CI: 7.5-not reached) in the non-statin group (P=0.058). NSCLC patients previously treated with nivolumab who were administered statins exhibited an increased response rate and longer TTF. This response was not statistically significant in OS.
有许多因素被认为可预测纳武单抗治疗非小细胞肺癌（NSCLC）的疗效，然而，尚无足够证据确定单一因素能预测纳武单抗的疗效。随着癌症治疗生物标志物研究的进展，据推测某些临床因素在预测化疗结果时起重要作用。对2016年至2017年接受纳武单抗治疗的67例NSCLC患者进行了前瞻性研究。将年龄、性别、东部肿瘤协作组体能状态、组织学类型、表皮生长因子受体（EGFR）突变、化疗史、吸烟状况、他汀类药物使用情况、贝特类药物使用情况、二肽基肽酶-4（DPP-4）抑制剂使用情况以及二甲双胍使用情况作为临床因素进行研究。采用Kaplan-Meier法进行统计分析，并对危险因素进行Cox回归分析，评估67例患者的肿瘤反应。患者的中位年龄为6岁（范围36-87岁），纳入46例男性和21例女性；体能状态0/1的有59例。病例分为腺癌（n=41）、鳞状细胞癌（n=17）和其他（n=9）。共有13例患者（19.4%）存在EGFR突变。这些临床因素在总生存期（OS）方面无统计学意义。还分析了临床实验室检查结果、并发症以及包括抗糖尿病或血脂异常药物在内的药物使用情况。他汀类药物在反应方面具有统计学意义（P=0.02）。使用他汀类药物组未达到治疗失败时间（TTF）[95%置信区间（CI）：1.9-未达到]，非他汀类药物组为4.0个月（95%CI：2.0-5.4）（P=0.039）。使用他汀类药物组的中位OS未达到（95%CI：8.7-未达到），非他汀类药物组为16.5个月（95%CI：7.5-未达到）（P=0.058）。先前接受纳武单抗治疗且使用他汀类药物的NSCLC患者表现出更高的反应率和更长的TTF。这种反应在OS方面无统计学意义。
