当前位置:科学网首页 > 小柯机器人 >详情
纳武单抗单独或联合伊匹单抗辅助治疗IV期黑色素瘤患者疗效显著
作者:小柯机器人 发布时间:2020/5/20 15:30:57

德国埃森大学医院Dirk Schadendorf在研究中取得进展。他们对纳武单抗单独或联合伊匹单抗辅助治疗无疾病证据的IV期黑色素瘤患者的疗效和安全性进行了分析。相关论文于2020年5月16日发表在《柳叶刀》杂志上。

纳武单抗和伊匹单抗单独或联合使用,可广泛用于晚期(即不可切除或转移性)黑色素瘤患者的免疫治疗。然而,该标准排除了无疾病证据的IV期黑色素瘤患者。

研究组在德国20个学术医疗中心进行了一项随机、双盲、安慰剂对照的2期临床试验,2015年9月2日至2018年11月20日,共招募了167名患有IV期黑色素瘤的18-80岁的患者,在手术或放疗后均无疾病迹象。将其按1:1:1随机分配,其中56名接受纳武单抗+伊匹单抗治疗,59名接受单独纳武单抗治疗,52名接受安慰剂治疗。

截至2019年7月2日,在中位随访28.4个月后,纳武单抗+伊匹单抗组未达到中位无复发生存期,纳武单抗组的中位无复发生存期为12.4个月,安慰剂组为6.4个月。纳武单抗+伊匹单抗组与安慰剂组的复发风险比为0.23,纳武单抗组与安慰剂组的复发风险比为0.56。

纳武单抗+伊匹单抗组的1年无复发生存率为75%,2年无复发生存率为70%;纳武单抗组分别为52%和42%;安慰剂组则分别为32%和14%。纳武单抗+伊匹单抗组中有71%的患者发生治疗相关的3-4级不良事件,而在纳武单抗组中有27%。

纳武单抗+伊匹单抗组中与治疗有关的任何级别不良事件导致62%的患者终止治疗,纳武单抗组有13%。据报道有3例患者因不良事件而死亡,但被认为与研究治疗无关。

综上,纳武单抗单独或联合伊匹单抗辅助治疗无疾病证据的IV期黑色素瘤患者,与安慰剂相比,无复发生存率显著增加,但3-4级不良事件发生率较高。

附:英文原文

Title: Adjuvant nivolumab plus ipilimumab or nivolumab monotherapy versus placebo in patients with resected stage IV melanoma with no evidence of disease (IMMUNED): a randomised, double-blind, placebo-controlled, phase 2 trial

Author: Lisa Zimmer, Elisabeth Livingstone, Jessica C Hassel, Michael Fluck, Thomas Eigentler, Carmen Loquai, Sebastian Haferkamp, Ralf Gutzmer, Friedegund Meier, Peter Mohr, Axel Hauschild, Bastian Schilling, Christian Menzer, Felix Kieker, Edgar Dippel, Alexander Rsch, Jan-Christoph Simon, Beate Conrad, Silvia Krner, Christine Windemuth-Kieselbach, Leonora Schwarz, Claus Garbe, Jürgen C Becker, Dirk Schadendorf, Carola Berking, Rudolf A Herbst, Uwe M Martens, Sabine Sell, Rudolf Stadler, Patrick Terheyden, Jochen Utikal

Issue&Volume: 2020/05/16

Abstract: Background

Nivolumab and ipilimumab, alone or in combination, are widely used immunotherapeutic treatment options for patients with advanced—ie, unresectable or metastatic—melanoma. This criterion, however, excludes patients with stage IV melanoma with no evidence of disease. We therefore aimed to evaluate the safety and efficacy of adjuvant nivolumab plus ipilimumab or nivolumab monotherapy versus a placebo in this patient population.

Methods

We did a randomised, double-blind, placebo-controlled, phase 2 trial in 20 German academic medical centres. Eligible patients were aged 18–80 years with stage IV melanoma with no evidence of disease after surgery or radiotherapy. Key exclusion criteria included uveal or mucosal melanoma, previous therapy with checkpoint inhibitors, and any previous immunosuppressive therapy within the 30 days before study drug administration. Eligible patients were randomly assigned (1:1:1), using a central, interactive, online system, to the nivolumab plus ipilimumab group (1 mg/kg of intravenous nivolumab every 3 weeks plus 3 mg/kg of intravenous ipilimumab every 3 weeks for four doses, followed by 3 mg/kg of nivolumab every 2 weeks), nivolumab monotherapy group (3 mg/kg of intravenous nivolumab every 2 weeks plus ipilimumab-matching placebo during weeks 1–12), or double-matching placebo group. The primary endpoint was the recurrence-free survival in the intention-to-treat population. The results presented in this report reflect the prespecified interim analysis of recurrence-free survival after 90 events had been reported. This study is registered with ClinicalTrials.gov, NCT02523313, and is ongoing.

Findings

Between Sept 2, 2015, and Nov 20, 2018, 167 patients were randomly assigned to receive nivolumab plus ipilimumab (n=56), nivolumab (n=59), or placebo (n=52). As of July 2, 2019, at a median follow-up of 28·4 months (IQR 17·7–36·8), median recurrence-free survival was not reached in the nivolumab plus ipilimumab group, whereas median recurrence-free survival was 12·4 months (95% CI 5·3–33·3) in the nivolumab group and 6·4 months (3·3–9·6) in the placebo group. The hazard ratio for recurrence for the nivolumab plus ipilimumab group versus placebo group was 0·23 (97·5% CI 0·12–0·45; p<0·0001), and for the nivolumab group versus placebo group was 0·56 (0·33–0·94; p=0·011). In the nivolumab plus ipilimumab group, recurrence-free survival at 1 year was 75% (95% CI 61·0–84·9) and at 2 years was 70% (55·1–81·0); in the nivolumab group, 1-year recurrence-free survival was 52% (38·1–63·9) and at 2 years was 42% (28·6–54·5); and in the placebo group, this rate was 32% (19·8–45·3) at 1 year and 14% (5·9–25·7) at 2 years. Treatment-related grade 3–4 adverse events were reported in 71% (95% CI 57–82) of patients in the nivolumab plus ipilimumab group and in 27% (16–40) of those in the nivolumab group. Treatment-related adverse events of any grade led to treatment discontinuation in 34 (62%) of 55 patients in the nivolumab plus ipilimumab group and seven (13%) of 56 in the nivolumab group. Three deaths from adverse events were reported but were considered unrelated to the study treatment.

Interpretation

Adjuvant therapy with nivolumab alone or in combination with ipilimumab increased recurrence-free survival significantly compared with placebo in patients with stage IV melanoma with no evidence of disease. The rates of grade 3–4 treatment-related adverse events in both active treatment groups were higher than the rates reported in previous pivotal trials done in advanced melanoma with measurable disease.

DOI: 10.1016/S0140-6736(20)30417-7

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30417-7/fulltext

期刊信息

LANCET:《柳叶刀》,创刊于1823年。隶属于爱思唯尔出版社,最新IF:59.102
官方网址:http://www.thelancet.com/
投稿链接:http://ees.elsevier.com/thelancet