一项关于他喹莫德维持治疗转移性去势抵抗性前列腺癌患者的随机、双盲、安慰剂对照II期研究，这些患者对一线多西他赛化疗有反应或病情稳定。
A randomized, double-blind, placebo-controlled phase II study of maintenance therapy with tasquinimod in patients with metastatic castration-resistant prostate cancer responsive to or stabilized during first-line docetaxel chemotherapy.
作者信息
Fizazi K, Ulys A, Sengeløv L, Moe M, Ladoire S, Thiery-Vuillemin A, Flechon A, Guida A, Bellmunt J, Climent M A, Chowdhury S, Dumez H, Matouskova M, Penel N, Liutkauskiene S, Stachurski L, Sternberg C N, Baton F, Germann N, Daugaard G
机构信息
Department of Cancer Medicine, Gustave Roussy, Université Paris-Saclay, Villejuif, France.
National Cancer Institute, Vilnius, Lithuania.
出版信息
Ann Oncol. 2017 Nov 1;28(11):2741-2746. doi: 10.1093/annonc/mdx487.
BACKGROUND
This phase II study was conducted to assess clinical efficacy of tasquinimod maintenance therapy in patients with metastatic castrate-resistant prostate cancer not progressing during first-line docetaxel-based therapy.
PATIENTS AND METHODS
Patients were randomly assigned (1 : 1) to receive tasquinimod (0.25-1.0 mg/day orally) or placebo. The primary end point was radiologic progression-free survival (rPFS); secondary efficacy end points included: overall survival (OS); PFS on next-line therapy (PFS 2) and symptomatic PFS, assessed using the Brief Pain Inventory (BPI) questionnaire and analgesic use. Quality of life was measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire and by the EuroQol-5 Dimension Quality of Life Instrument (EQ-5D). Adverse events were recorded.
RESULTS
A total of 219 patients were screened and 144 patients randomized. The median duration of treatment was 18.7 weeks (range 0.6-102.7 weeks) for the tasquinimod arm and 19.2 weeks (range 0.4-80.0 weeks) for the placebo arm. Median (90% CI) rPFS was 31.7 (24.3-53.7) and 22.7 (16.1-25.9) weeks in the tasquinimod and placebo arms, respectively [HR (90% CI) 0.6 (0.4-0.9), P = 0.0162]. The median OS was not reached because only 14 deaths occurred by the cut-off date. No statistically significant differences between treatment arms were noted for symptomatic PFS, PFS 2, BPI score, FACT-P score, or EQ-5D. The incidence of any treatment emergent adverse event (TEAE) was similar in the tasquinimod and placebo arms (97.2% versus 94.3%, respectively), whereas severe TEAEs (NCI-CTC Grade 3-5) incidence was higher in the tasquinimod group (50.7% versus 27.1%).
CONCLUSIONS
Randomized trials testing new drugs as maintenance can be successfully conducted after chemotherapy in castrate-resistant prostate cancer. Maintenance tasquinimod therapy significantly reduced the risk of rPFS by 40%.
CLINICALTRIALS
gov identifier NCT01732549.
背景
本II期研究旨在评估他喹莫德维持治疗对一线多西他赛治疗期间未进展的转移性去势抵抗性前列腺癌患者的临床疗效。
患者与方法
患者被随机分配（1:1）接受他喹莫德（口服0.25 - 1.0mg/天）或安慰剂。主要终点是影像学无进展生存期（rPFS）；次要疗效终点包括：总生存期（OS）；二线治疗的无进展生存期（PFS2）和症状性无进展生存期，使用简明疼痛量表（BPI）问卷和镇痛药使用情况进行评估。生活质量通过癌症治疗功能评估 - 前列腺（FACT - P）问卷和欧洲五维健康量表（EQ - 5D）进行测量。记录不良事件。
结果
共筛选219例患者，144例患者随机分组。他喹莫德组的中位治疗持续时间为18.7周（范围0.6 - 102.7周），安慰剂组为19.2周（范围0.4 - 80.0周）。他喹莫德组和安慰剂组的中位（90%CI）rPFS分别为31.7（24.3 - 53.7）周和22.7（16.1 - 25.9）周[风险比（90%CI）0.6（0.4 - 0.9），P = 0.0162]。由于截止日期时仅发生14例死亡，因此未达到中位OS。在症状性无进展生存期、PFS2、BPI评分、FACT - P评分或EQ - 5D方面，各治疗组之间未观察到统计学上的显著差异。他喹莫德组和安慰剂组的任何治疗突发不良事件（TEAE）发生率相似（分别为97.2%和94.3%），而他喹莫德组严重TEAE（NCI - CTC 3 - 5级）的发生率更高（50.7%对27.1%）。
结论
在去势抵抗性前列腺癌化疗后可以成功开展测试新药作为维持治疗的随机试验。他喹莫德维持治疗可使rPFS风险显著降低40%。
临床试验
gov标识符NCT01732549。
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