靶向CD30的抗体耦联新药治疗皮肤T细胞瘤淋巴瘤:三期临床试验,成功

Lancet

2017-06-06Article

47.831

影响因子

原标题:Brentuximab vedotin或医生选择治疗CD30阳性皮肤T细胞淋巴瘤(ALCANZA):国际、多中心、开放性、随机、III期临床研究

① 13个国家,52个中心,自2012年8月13日至2015年7月31日,总计131例复治CD30阳性蕈样肉芽肿或原发性皮肤间变性大细胞淋巴瘤患者入组;② 1:1随机,brentuximab vedotin 1.8 mg/kg静脉注射,每3周一周期,直到16个周期,或医生选择口服甲氨蝶呤每日5-50 mg或口服贝沙罗汀每日300 mg/m(2)直到48周;③ 中位随访22.9个月,获得客观缓解持续4个月的比例分别为56.3%和12.5%;④ 3-4度不良事件分别为41%和47%,两组间神经毒性发生率分别为67%和6%。

皮肤T细胞淋巴瘤 Brentuximab vedotin单抗 贝沙罗汀 神经毒性 蕈样肉芽肿 皮肤间变性大细胞淋巴瘤

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Title:
Brentuximab vedotin or physician's choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial

DOI:
10.1016/S0140-6736(17)31266-7

Abstract & Authors展开

Abstract:
Cutaneous T-cell lymphomas are rare, generally incurable, and associated with reduced quality of life. Present systemic therapies rarely provide reliable and durable responses. We aimed to assess efficacy and safety of brentuximab vedotin versus conventional therapy for previously treated patients with CD30-positive cutaneous T-cell lymphomas. In this international, open-label, randomised, phase 3, multicentre trial, we enrolled adult patients with CD30-positive mycosis fungoides or primary cutaneous anaplastic large-cell lymphoma who had been previously treated. Patients were enrolled across 52 centres in 13 countries. Patients were randomly assigned (1:1) centrally by an interactive voice and web response system to receive intravenous brentuximab vedotin 1·8 mg/kg once every 3 weeks, for up to 16 3-week cycles, or physician's choice (oral methotrexate 5-50 mg once per week or oral bexarotene 300 mg/m(2) once per day) for up to 48 weeks. The primary endpoint was the proportion of patients in the intention-to-treat population achieving an objective global response lasting at least 4 months per independent review facility. Safety analyses were done in all patients who received at least one dose of study drug. This trial was registered with ClinicalTrials.gov, number NCT01578499. Between Aug 13, 2012, and July 31, 2015, 131 patients were enrolled and randomly assigned to a group (66 to brentuximab vedotin and 65 to physician's choice), with 128 analysed in the intention-to-treat population (64 in each group). At a median follow-up of 22·9 months (95% CI 18·4-26·1), the proportion of patients achieving an objective global response lasting at least 4 months was 56·3% (36 of 64 patients) with brentuximab vedotin versus 12·5% (eight of 64) with physician's choice, resulting in a between-group difference of 43·8% (95% CI 29·1-58·4; p<0·0001). Grade 3-4 adverse events were reported in 27 (41%) of 66 patients in the brentuximab vedotin group and 29 (47%) of 62 patients in the physician's choice group. Peripheral neuropathy was seen in 44 (67%) of 66 patients in the brentuximab vedotin group (n=21 grade 2, n=6 grade 3) and four (6%) of 62 patients in the physician's choice group. One of the four on-treatment deaths was deemed by the investigator to be treatment-related in the brentuximab vedotin group; no on-treatment deaths were reported in the physician's choice group. Significant improvement in objective response lasting at least 4 months was seen with brentuximab vedotin versus physician's choice of methotrexate or bexarotene. Millennium Pharmaceuticals Inc (a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd), Seattle Genetics Inc.

All Authors:
H Miles Prince,Youn H Kim,Steven M Horwitz,Reinhard Dummer,Julia Scarisbrick,Pietro Quaglino,Pier Luigi Zinzani,Pascal Wolter,Jose A Sanches,Pablo L Ortiz-Romero,Oleg E Akilov,Larisa Geskin,Judith Trotman,Kerry Taylor,Stephane Dalle,Michael Weichenthal,Jan Walewski,David Fisher,Brigitte Dréno,Rudolf Stadler,Tatyana Feldman,Timothy M Kuzel,Yinghui Wang,Maria Corinna Palanca-Wessels,Erin Zagadailov,William L Trepicchio,Wenwen Zhang,Hui-Min Lin,Yi Liu,Dirk Huebner,Meredith Little,Sean Whittaker,Madeleine Duvic,

First Authors:
H Miles Prince,Youn H Kim

Correspondence:
H Miles Prince

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