Use of nivolumab in elderly patients with advanced squamous non-small-cell lung cancer: results from the Italian cohort of an expanded access programme.
AIM: This analysis evaluated the efficacy and safety of nivolumab,陆雨棠 an immune checkpoint inhibitor, in elderly patients with stage IIIB or IV squamous non-small-cell lung cancer (NSCLC) enrolled in the expanded access programme (EAP) in Italy. METHODS: Nivolumab was available on physician request. Safety data included adverse events (AEs). Efficacy data included investigator-assessed tumour response, progression date and survival information. Results were analysed for patients aged <65微奢 , 65-<75 and >/=75 years and for the overall population. RESULTS: A total of 371 patients with squamous NSCLC were enrolled at 96 centres between April 2015 and September 2015; 34% (n = 126), 47% (n = 175) and 19% (n = 70) were aged <65, 65-<75 and >/=75 years, respectively. Efficacy was similar among patients aged <65, 65-<75 and >/=75 years and the overall population (objective response rates: 18%, 18%, 19% and 18%玻璃拉拉, respectively; disease control rates: 49%, 47%, 43% and 47%东狮山 , respectively). Median overall survival was reduced in patients aged >/=75 years (5.8 months) versus patients aged <65; years (8.6 months), patients aged 65-<75 years (8.0 months) and the overall population (7.9 months). The incidence of grade 3-4 treatment-related AEs was low in patients aged 65, 65-<75 and >/=75 years and the overall population (3%, 9%, 3%, 6%, respectively). Discontinuation rates due to treatment-related AEs were low irrespective of age (4-5%). CONCLUSIONS: These EAP results suggest that elderly patients with advanced squamous NSCLC benefit from nivolumab, with tolerability similar to that in the overall population.
杂志：Eur J Cancer
该分析评估了纳武单抗治疗（一种免疫抑制剂检查点）对III期或IV期鳞状非小细胞肺癌（NSCLC）老年患者的疗效和安全性。纳武单抗治疗可以在医生的要求下使用房仕龙 。袁世凯后人 安全数据包括不良事件（AEs）。疗效数据包括研究者评估的肿瘤反应、进展日期和生存信息。结果显示姿媚堂 ，这些EAP结果提示老年晚期鳞状非小细胞肺癌患者受益于纳武单抗治疗，耐受性与总体人群相似。
CNS Efficacy of Osimertinib in Patients With T790M-Positive Advanced Non-Small-Cell Lung Cancer: Data From a Randomized Phase III Trial (AURA3).
Purpose In patients with epidermal growth factor receptor ( EGFR) mutation-positive advanced non-small-cell lung cancer (NSCLC), there is an unmet need for EGFR-tyrosine kinase inhibitors with improved CNS penetration and activity against CNS metastases, either at initial diagnosis or time of progression. We report the first comparative evidence of osimertinib CNS efficacy versus platinum-pemetrexed from a phase III study (AURA3; ClinicalTrials.gov identifier: NCT02151981) in patients with EGFR T790M-positive advanced NSCLC who experience disease progression with prior EGFR-tyrosine kinase inhibitor treatment. Methods Patients with asymptomatic, stable CNS metastases were eligible for enrollment and were randomly assigned 2:1 to osimertinib 80 mg once daily or platinum-pemetrexed. A preplanned subgroup analysis was conducted in patients with measurable and/or nonmeasurable CNS lesions on baseline brain scan by blinded independent central neuroradiological review. The CNS evaluable for response set included only patients with one or more measurable CNS lesions. The primary objective for this analysis was CNS objective response rate (ORR). Results Of 419 patients randomly assigned to treatment, 116 had measurable and/or nonmeasurable CNS lesions, including 46 patients with measurable CNS lesions. At data cutoff (April 15无限极萃雅 , 2016), CNS ORR in patients with one or more measurable CNS lesions was 70% (21 of 30; 95% CI, 51% to 85%) with osimertinib and 31% (5 of 16; 95% CI, 11% to 59%) with platinum-pemetrexed (odds ratio小薇吉他谱, 5.13; 95% CI, 1.44 to 20.64; P = .015); the ORR was 40% (30 of 75; 95% CI, 29% to 52%) and 17% (7 of 41; 95% CI, 7% to 32%), respectively固始房产网 , in patients with measurable and/or nonmeasurable CNS lesions (odds ratio易格英语 , 3.24; 95% CI, 1.33 to 8.81; P = .014). Median CNS duration of response in patients with measurable and/or nonmeasurable CNS lesions was 8.9 months (95% CI, 4.3 months to not calculable) for osimertinib and 5.7 months (95% CI, 4.4 to 5.7 months) for platinum-pemetrexed; median CNS progression-free survival was 11.7 months and 5.6 months, respectively (hazard ratio, 0.32; 95% CI, 0.15 to 0.69; P = .004). Conclusion Osimertinib demonstrated superior CNS efficacy versus platinum-pemetrexed in T790M-positive advanced NSCLC.
在表皮生长因子受体（EGFR）突变阳性的晚期非小细胞肺癌（NSCLC）患者中，EGFR-酪氨酸激酶抑制剂无论是在最初诊断还是在进展时，都有改善中枢神经系统渗透和抗中枢神经系统转移活性的需求未得到满足。该研究报告了在EGFR T790M阳性晚期NSCLC患者中使用EGFR-酪氨酸激酶抑制剂治疗后患有疾病进展的III期研究（AURA3; ClinicalTrials.gov标识符：NCT02151981）中osimertinib CNS疗效与铂 - 培美曲塞的比较证据。针对无症状的、稳定的中枢神经系统转移的患者，随机分配比例为2:1 ，每日注射一次80毫克激酶抑制剂或铂-培美曲塞极品少帅。在基线脑扫描中有可测量和不可测量中枢神经系统病变的患者中，通过盲法独立中枢神经放射学复查进行了预先计划的亚组分析。在随机分配治疗的419例患者中，116例存在可测量和不可测量的中枢神经系统病变，其中46例存在可测量的中枢神经系统病变。结果指出，激酶抑制剂对t790m阳性晚期NSCLC的CNS疗效优于铂培美曲塞小司考 。
Indoleamine 2,3-dioxygenase 1 and programmed cell death-ligand 1 co-expression correlates with aggressive features in lung adenocarcinoma.
BACKGROUND: Indoleamine 2叶可儿 ,3-dioxygenase 1 (IDO1) is an immunosuppressive effector, and its expression is associated with prognosis in several cancer types. Here前田阳菜 , we investigated the relationship between IDO1 expression in lung adenocarcinoma and patient prognosis and clinicopathological features, including programmed cell death-ligand 1 (PD-L1) expression. MATERIALS AND METHODS: In this study, surgically resected primary lung adenocarcinoma specimens from 427 patients were evaluated for IDO1 and PD-L1 expression by immunohistochemistry苦海女神龙 , and lung adenocarcinoma cell lines were evaluated for IDO1 and PD-L1 protein expression by enzyme-linked immunosorbent assay and flow cytometry and for messenger RNA levels by real-time reverse-transcriptase polymerase chain reaction analysis. RESULTS: IDO1 was expressed in 260 patients (60.9%) at 1% cut-off and 63 patients (14.8%) at 50% cut-off. Tissues from 145 patients (34.0%) were positive for PD-L1 using the cut-off of 1%. Multivariate analysis showed that >/=1% IDO1 positivity was significantly associated with higher tumour grade, vascular invasion and PD-L1 expression. IDO1 and PD-L1 proteins were co-expressed in 123 patients (28.8%), and co-expressing tumours exhibited significantly more malignant traits than those positive for one or neither protein. In multivariate analysis, co-expression of IDO1 and PD-L1 was significantly associated with shorter disease-free survival and overall survival. Both proteins were upregulated in lung adenocarcinoma cell lines by treatment with interferon-gamma and transforming growth factor-beta. CONCLUSION: These results suggest that IDO1 and PD-L1 co-expression may define an aggressive form of lung adenocarcinoma.
杂志：Eur J Cancer
吲哚胺2,3-双加氧酶1（IDO1） 是一种免疫抑制效应物，其表达与几种癌症类型的预后有关。在此葛粉的吃法 ，作者研究了肺腺癌中IDO1表达与患者预后及临床病理特征（包括程序性细胞死亡配体1 （PD-L1）表达）的关系。研究人员采用免疫组织化学方法对427例肺原发性腺癌标本进行手术切除后的IDO1和PD-L1表达情况进行评估，通过酶联免疫吸附试验和流式细胞术对肺腺癌细胞系IDO1和PD-L1表达情况进行评估兰希黎，通过实时反转录酶聚合酶链反应分析对信使RNA水平进行评估随爱沉沦。分别在1%的情况下戴维斯双杀 ，260名患者和在50%的情况下63名患者的患者飞跃长生 ，被表示为 “IDO1”。这些结果提示IDO1和PD-L1共同表达可能定义了肺腺癌的侵袭性形式。