初诊时的 Gleason 评分能否预测醋酸阿比特龙治疗转移性去势抵抗性前列腺癌患者的疗效？醋酸阿比特龙 III 期试验分析。
Does Gleason score at initial diagnosis predict efficacy of abiraterone acetate therapy in patients with metastatic castration-resistant prostate cancer? An analysis of abiraterone acetate phase III trials.
作者信息
Fizazi K, Flaig T W, Stöckle M, Scher H I, de Bono J S, Rathkopf D E, Ryan C J, Kheoh T, Li J, Todd M B, Griffin T W, Molina A, Ohlmann C H
机构信息
Institut Gustave Roussy, University of Paris Sud, Villejuif, France
University of Colorado Cancer Center, University of Colorado School of Medicine, Aurora, USA.
出版信息
Ann Oncol. 2016 Apr;27(4):699-705. doi: 10.1093/annonc/mdv545. Epub 2015 Nov 25.
BACKGROUND
The usefulness of Gleason score (<8 or ≥8) at initial diagnosis as a predictive marker of response to abiraterone acetate (AA) plus prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) was explored retrospectively.
PATIENTS AND METHODS
Initial diagnosis Gleason score was obtained in 1048 of 1195 (COU-AA-301, post-docetaxel) and 996 of 1088 (COU-AA-302, chemotherapy-naïve) patients treated with AA 1 g plus prednisone 5 mg twice daily by mouth or placebo plus prednisone. Efficacy end points included radiographic progression-free survival (rPFS) and overall survival (OS). Distributions and medians were estimated by Kaplan-Meier method and hazard ratio (HR) and 95% confidence interval (CI) by Cox model.
RESULTS
Baseline characteristics were similar across studies and treatment groups. Regardless of Gleason score, AA treatment significantly improved rPFS in post-docetaxel [Gleason score <8: median, 6.4 versus 5.5 months (HR = 0.70; 95% CI 0.56-0.86), P = 0.0009 and Gleason score ≥8: median, 5.6 versus 2.9 months (HR = 0.58; 95% CI 0.48-0.72), P < 0.0001] and chemotherapy-naïve patients [Gleason score <8: median, 16.5 versus 8.2 months (HR = 0.50; 95% CI 0.40-0.62), P < 0.0001 and Gleason score ≥8: median, 13.8 versus 8.2 months (HR = 0.61; 95% CI 0.49-0.76), P < 0.0001]. Clinical benefit of AA treatment was also observed for OS, prostate-specific antigen (PSA) response, objective response and time to PSA progression across studies and Gleason score subgroups.
CONCLUSION
OS and rPFS trends demonstrate AA treatment benefit in patients with pre- or post-chemotherapy mCRPC regardless of Gleason score at initial diagnosis. The initial diagnostic Gleason score in patients with mCRPC should not be considered in the decision to treat with AA, as tumour metastases may no longer reflect the histology at the time of diagnosis.
CLINICAL TRIALS NUMBER
COU-AA-301 (NCT00638690); COU-AA-302 (NCT00887198).
背景
回顾性探讨了初诊时 Gleason 评分（<8 或≥8）作为转移性去势抵抗性前列腺癌（mCRPC）患者醋酸阿比特龙（AA）加泼尼松治疗反应预测指标的有效性。
患者与方法
在接受每日口服 1 g AA 加 5 mg 泼尼松或安慰剂加泼尼松治疗的 1195 例患者中的 1048 例（COU-AA-301，多西他赛治疗后）和 1088 例患者中的 996 例（COU-AA-302，未接受过化疗）中获取初诊时的 Gleason 评分。疗效终点包括影像学无进展生存期（rPFS）和总生存期（OS）。采用 Kaplan-Meier 方法估计分布和中位数，采用 Cox 模型估计风险比（HR）和 95%置信区间（CI）。
结果
各研究和治疗组的基线特征相似。无论 Gleason 评分如何，AA 治疗均显著改善了多西他赛治疗后的患者的 rPFS[Gleason 评分<8：中位数，6.4 个月对 5.5 个月（HR = 0.70；95%CI 0.56 - 0.86），P = 0.0009；Gleason 评分≥8：中位数，5.6 个月对 2.9 个月（HR = 0.58；95%CI 0.48 - 0.72），P < 0.0001]以及未接受过化疗的患者的 rPFS[Gleason评分<8：中位数，16.5 个月对 8.2 个月（HR = 0.50；95%CI 0.40 - 0.62），P < 0.0001；Gleason 评分≥8：中位数，13.8 个月对 8.2 个月（HR = 0.61；95%CI 0.49 - 0.76），P < 0.0001]。在各项研究和 Gleason 评分亚组中，还观察到 AA 治疗对 OS（总生存期）、前列腺特异性抗原（PSA）反应、客观反应以及 PSA 进展时间的临床获益。
结论
OS 和 rPFS 趋势表明，无论初诊时的 Gleason 评分如何，AA 治疗对化疗前或化疗后的 mCRPC 患者均有益。mCRPC 患者初诊时的 Gleason 评分不应作为决定是否采用 AA 治疗的考虑因素，因为肿瘤转移可能不再反映诊断时的组织学情况。
临床试验编号
COU-AA-301（NCT00638690）；COU-AA-302（NCT00887198）。
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