NGR-hTNF结合最好的调查员选择以前治疗恶性胸膜间皮瘤(NGR015):一个随机,双盲,安慰剂对照3期临床试验。

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Gregorc V, Gaafar RM, Favaretto Grossi F,前来J, Polychronis, Bidoli P, Tiseo M,沙R,泰勒P,由年代,Muzio, Bearz, Greillier L,丰塔纳F, G Salini, Lambiase, O ' brien M

NGR-hTNF结合最好的调查员选择以前治疗恶性胸膜间皮瘤(NGR015):一个随机,双盲,安慰剂对照3期临床试验。

柳叶刀杂志。2018年6月,19 (6):799 - 811。doi: 10.1016 / s1470 - 2045 (18) 30193 - 1。2018年5月9日Epub。

PubMed ID

29753703 (在PubMed

]

文摘

背景:恶性胸膜间皮瘤是一种侵略性的癌症与高度vascularised肿瘤。它有不良预后和一些一线化疗失败后的治疗方案。NGR-hTNF vascular-targeting药物增加渗透的瘤内化疗和t细胞渗透通过修改肿瘤微环境。在这个试验中,我们旨在调查的有效性和安全性NGR-hTNF恶性胸膜间皮瘤患者进展一线治疗期间或之后。方法:NGR015是一个随机、双盲、安慰剂对照3期临床试验在41中心在12个国家。合格的参与者恶性胸膜间皮瘤的组织学亚型(上皮肉瘤样的,或混合),18岁以上,有一个东部合作肿瘤组性能状态0 - 2和放射检查记录进步的疾病后pemetrexed-based化疗方案。参与者被随机分配接受每周NGR-hTNF 0.8杯/ m(2)静脉注射+最好的侦探的选择(n = 200),或安慰剂+最好的侦探的选择(n = 200)。最好的侦探选择是决定之前随机分配,可以单药吉西他滨(1000 - 1250 mg / m(2)静脉注射),vinorelbine(25毫克/米(2)静脉注射或60毫克/米(2)口头),阿霉素(60 - 75毫克/米(2)静脉注射),或最好的支持性护理。病人被随机(1:1),四块大小分层后的性能状态和选择最好的侦探。主要研究终点是整体生存意向处理人口。 The trial is closed to new participants and is registered with ClinicalTrials.gov (NCT01098266). FINDINGS: Between April 12, 2010 and Jan 21, 2013, we enrolled 400 eligible participants. 381 (95%) of 400 patients were selected to receive chemotherapy before all participants were randomly assigned to receive NGF-hTNF plus best investigator choice (n=200) or placebo plus best investigator choice (n=200). At the cutoff date (April 29, 2014), the median follow-up was 18.7 months (IQR 15.1-24.4), and overall survival did not differ between the two treatment groups (median 8.5 months [95% CI 7.2-9.9] in the NGR-hTNF group vs 8.0 months [6.6-8.9] in the placebo group; hazard ratio 0.94, 95% CI 0.75-1.18; p=0.58). Grade 3 or worse study-emergent adverse events occurred in 136 (70%) of patients receiving NGR-hTNF versus 118 (61%) of patients receiving placebo, with the most common being neutropenia (35 [18%] of 193 patients vs 36 [19%] of 193 patients), pain (11 [6%] vs 16 [8%]), dyspnoea (nine [5%] vs seven [4%]), and chills (nine [5%] vs none). 50 (26%) patients in the NGR-hTNF group had a serious adverse event, compared with 47 (24%) in the placebo group. Treatment-related serious adverse events occurred in 17 (9%) patients in the NGR-hTNF group and 20 patients (10%) in the placebo group. There were 12 deaths in the NGR-hTNF group and 13 deaths in the placebo group, but none were treatment related. INTERPRETATION: The study did not meet its primary endpoint. The hypothesis-generating findings from the subgroup analyses deserve a confirmatory randomised trial because patients who rapidly progress after first-line treatment have a poor prognosis. FUNDING: MolMed.

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