DCVAC/PCa是一种积极的细胞免疫疗法，旨在启动针对前列腺癌的免疫反应。评价DCVAC/PCa联合化疗后DCVAC/PCa维持治疗转移性去势抵抗性前列腺癌(mCRPC)的疗效和安全性。

可行的双盲、平行组、安慰剂对照、三期随机临床试验招募了2014年6月至2017年11月期间美国和欧洲177家医院诊所的mCRPC患者。数据分析从2019年12月至2020年7月进行。

共有1182名mCRPC患者(中位[范围]年龄68[46-89]岁)被随机分为DCVAC/PCa组(n = 787)或安慰剂组(n = 395)。其中610例(81.8%)患者开始DCVAC/PCa治疗，376例(98.4%)患者开始安慰剂治疗。在所有随机患者中，DCVAC/PCa组和安慰剂组的OS无差异(中位OS, 23.9个月[95% CI, 21.6-25.3] vs 24.3个月[95% CI, 22.6-26.0];风险比，1.04;95% ci, 0.90-1.21;P = .60)。未观察到次要疗效终点(放射无进展生存期、前列腺特异性抗原进展时间或骨骼相关事件)的差异。与DCVAC/PCa或安慰剂相关的治疗紧急不良事件分别发生在749例(9.2%)和379例(12.7%)患者中的69例和48例。最常见的治疗紧急不良事件(DCVAC/PCa [n = 749] vs安慰剂[n = 379])是疲劳(271 [36.2%]vs 152[40.1%])、脱发(222 [29.6%]vs 130[34.3%])和腹泻(206 [27.5%]vs 117[30.9%])。在这项3期随机临床试验中，DCVAC/PCa联合多西他赛+泼尼松并继续作为维持治疗，并未延长mCRPC患者的OS，且耐受性良好。

Abstract

Importance: DCVAC/PCa is an active cellular immunotherapy designed to initiate an immune response against prostate cancer.

Objective: To evaluate the efficacy and safety of DCVAC/PCa plus chemotherapy followed by DCVAC/PCa maintenance treatment in patients with metastatic castration-resistant prostate cancer (mCRPC).

Design, setting, and participants: The VIABLE double-blind, parallel-group, placebo-controlled, phase 3 randomized clinical trial enrolled patients with mCRPC among 177 hospital clinics in the US and Europe between June 2014 and November 2017. Data analyses were performed from December 2019 to July 2020.

Interventions: Eligible patients were randomized (2:1) to receive DCVAC/PCa (add-on and maintenance) or placebo, both in combination with chemotherapy (docetaxel plus prednisone). The stratification was applied according to geographical region (US or non-US), prior therapy (abiraterone, enzalutamide, or neither), and Eastern Cooperative Oncology Group performance status (0-1 or 2). DCVAC/PCa or placebo was administered subcutaneously every 3 to 4 weeks (up to 15 doses).

Main outcomes and measures: The primary outcome was overall survival (OS), defined as the time from randomization until death due to any cause, in all randomized patients. Survival was compared using 2-sided log-rank test stratified by geographical region, prior therapy with abiraterone and/or enzalutamide, and Eastern Cooperative Oncology Group performance status.

Results: A total of 1182 men with mCRPC (median [range] age, 68 [46-89] years) were randomized to receive DCVAC/PCa (n = 787) or placebo (n = 395). Of these, 610 (81.8%) started DCVAC/PCa, and 376 (98.4%) started placebo. There was no difference in OS between the DCVAC/PCa and placebo groups in all randomized patients (median OS, 23.9 months [95% CI, 21.6-25.3] vs 24.3 months [95% CI, 22.6-26.0]; hazard ratio, 1.04; 95% CI, 0.90-1.21; P = .60). No differences in the secondary efficacy end points (radiological progression-free survival, time to prostate-specific antigen progression, or skeletal-related events) were observed. Treatment-emergent adverse events related to DCVAC/PCa or placebo occurred in 69 of 749 (9.2%) and 48 of 379 (12.7%) patients, respectively. The most common treatment-emergent adverse events (DCVAC/PCa [n = 749] vs placebo [n = 379]) were fatigue (271 [36.2%] vs 152 [40.1%]), alopecia (222 [29.6%] vs 130 [34.3%]), and diarrhea (206 [27.5%] vs 117 [30.9%]).

Conclusions and relevance: In this phase 3 randomized clinical trial, DCVAC/PCa combined with docetaxel plus prednisone and continued as maintenance treatment did not extend OS in patients with mCRPC and was well tolerated.

原文链接

pubmed.ncbi.nlm.nih.gov/35142815/

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