Background

In the COU-AA-302 study (NCT00887198), abiraterone acetate plus prednisone (AAP) significantly improved outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) versus prednisone alone. Baseline clinical parameters predicting that treatment response could help inform clinical decisions were explored.

Objective

To identify patients who derive the greatest clinical benefit from AAP treatment.

Design, setting, and participants

A total of 1088 mCRPC patients treated with either AAP or prednisone in the first-line setting in COU-AA-302 were included in this post hoc analysis.

Intervention

Abiraterone acetate1000 mg daily versus placebo, both plus prednisone 10 mg daily.

Outcome measurements and statistical analysis

Univariate and multivariable Cox regression analyses were performed, including clinical and pathological parameters for the primary end points overall survival (OS) and radiographic progression-free survival (rPFS), and secondary study end points. Tumor-associated baseline parameters independently impacting OS were applied to stratify patients according to possible treatment effects.

Results and limitations

Baseline prostate-specific antigen (PSA), tumor-related pain as assessed by the Brief Pain Inventory-Short Form (BPI-SF), and Gleason score (GS) at primary diagnosis were identified as tumor-associated variables that independently impacted OS. AAP significantly improved outcomes versus prednisone in both group 1 (BPI-SF 0–1 and PSA <80 ng/ml and GS <8; p = 0.006; hazard ratio [HR]: 0.61) and group 2 (BPI-SF 2–3 and/or PSA ≥80 ng/ml and/or GS ≥8; p = 0.03; HR: 0.84). The differences observed for treatment effects between groups 1 and 2 for OS (HR: 0.61 vs 0.84), rPFS (HR: 0.41 vs 0.59), and time to chemotherapy (HR: 0.64 vs 0.71) were not statistically significant.

Conclusions

AAP significantly improved outcomes in mCRPC patients compared with prednisone alone regardless of baseline pain and PSA level, and GS at primary diagnosis with no significant differences between observed treatment effects in groups 1 and 2.

Patient summary

Treatment with abiraterone acetate and prednisone (compared with treatment with prednisone only) for metastatic castration-resistant prostate cancer increased survival in all patients in the study regardless of pain, prostate-specific antigen levels at the start of treatment, and Gleason score at primary diagnosis.

中文翻译：

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初治转移性去势抵抗性前列腺癌男性中醋酸阿比特龙+泼尼松的3期COU-AA-302研究：基于疼痛，前列腺特异性抗原和格里森评分的分层分析

背景

在COU-AA-302研究（NCT00887198）中，乙酸阿比特龙酯联合泼尼松（AAP）与单纯的泼尼松相比可显着改善转移性去势抵抗性前列腺癌（mCRPC）患者的预后。基线临床参数预测治疗反应可以帮助指导临床决策进行了探讨。

客观的

识别从AAP治疗中获得最大临床益处的患者。

设计，设置和参与者

在此事后分析中，总共包括1088例在COU-AA-302一线治疗中接受AAP或泼尼松治疗的mCRPC患者。

干涉

醋酸阿比特龙1000毫克/天与安慰剂，两者加泼尼松10毫克/天。

成果测量和统计分析

进行了单变量和多变量Cox回归分析，包括主要终点的总生存期（OS）和放射学无进展生存期（rPFS）的临床和病理参数，以及次要研究终点。根据可能的治疗效果，应用独立影响OS的与肿瘤相关的基线参数对患者进行分层。

结果与局限性

基线前列腺特异性抗原（PSA），通过简短疼痛库存量-简短形式（BPI-SF）评估的肿瘤相关疼痛和初诊时的格里森评分（GS）被确定为独立影响OS的肿瘤相关变量。在第1组（BPI-SF 0-1和PSA <80 ng / ml和GS <8；p  = 0.006；危险比[HR]：0.61）和第2组（BPI-SF 2– 3和/或PSA≥80ng / ml和/或GS≥8；p  = 0.03； HR：0.84）。在第1组和第2组之间观察到的OS（HR：0.61 vs 0.84），rPFS（HR：0.41 vs 0.59）和化疗时间（HR：0.64 vs 0.71）的治疗效果差异无统计学意义。

结论

无论基线疼痛和PSA水平如何，与单独的泼尼松相比，AC均可显着改善mCRPC患者的预后，无论基线疼痛和PSA水平如何，以及初诊时的GS，在第1组和第2组中观察到的治疗效果之间均无显着差异。

病人总结

用乙酸阿比特龙酯和强的松治疗（与仅使用泼尼松治疗）相比，转移性去势抵抗性前列腺癌可提高研究中所有患者的生存率，而不论疼痛，治疗开始时前列腺特异性抗原水平以及初次诊断时的格里森评分如何。