多西他赛治疗非转移性前列腺癌：STAMPEDE 随机对照试验的长期生存结果。
Docetaxel for Nonmetastatic Prostate Cancer: Long-Term Survival Outcomes in the STAMPEDE Randomized Controlled Trial.
机构信息
Division of Radiotherapy and Imaging, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, UK.
MRC Clinical Trials Unit at University College London (UCL), Institute of Clinical Trials and Methodology, UCL, London, UK.
出版信息
JNCI Cancer Spectr. 2022 Jul 1;6(4). doi: 10.1093/jncics/pkac043.
BACKGROUND
STAMPEDE previously reported adding upfront docetaxel improved overall survival for prostate cancer patients starting long-term androgen deprivation therapy. We report long-term results for non-metastatic patients using, as primary outcome, metastatic progression-free survival (mPFS), an externally demonstrated surrogate for overall survival.
METHODS
Standard of care (SOC) was androgen deprivation therapy with or without radical prostate radiotherapy. A total of 460 SOC and 230 SOC plus docetaxel were randomly assigned 2:1. Standard survival methods and intention to treat were used. Treatment effect estimates were summarized from adjusted Cox regression models, switching to restricted mean survival time if non-proportional hazards. mPFS (new metastases, skeletal-related events, or prostate cancer death) had 70% power (α = 0.05) for a hazard ratio (HR) of 0.70. Secondary outcome measures included overall survival, failure-free survival (FFS), and progression-free survival (PFS: mPFS, locoregional progression).
RESULTS
Median follow-up was 6.5 years with 142 mPFS events on SOC (3 year and 54% increases over previous report). There was no good evidence of an advantage to SOC plus docetaxel on mPFS (HR = 0.89, 95% confidence interval [CI] = 0.66 to 1.19; P = .43); with 5-year mPFS 82% (95% CI = 78% to 87%) SOC plus docetaxel vs 77% (95% CI = 73% to 81%) SOC. Secondary outcomes showed evidence SOC plus docetaxel improved FFS (HR = 0.70, 95% CI = 0.55 to 0.88; P = .002) and PFS (nonproportional P = .03, restricted mean survival time difference = 5.8 months, 95% CI = 0.5 to 11.2; P = .03) but no good evidence of overall survival benefit (125 SOC deaths; HR = 0.88, 95% CI = 0.64 to 1.21; P = .44). There was no evidence SOC plus docetaxel increased late toxicity: post 1 year, 29% SOC and 30% SOC plus docetaxel grade 3-5 toxicity.
CONCLUSIONS
There is robust evidence that SOC plus docetaxel improved FFS and PFS (previously shown to increase quality-adjusted life-years), without excess late toxicity, which did not translate into benefit for longer-term outcomes. This may influence patient management in individual cases.
背景
STAMPEDE 此前报道称，对于开始长期雄激素剥夺治疗的前列腺癌患者，提前使用多西他赛可提高总生存率。我们报告了使用非转移性患者的长期结果，以转移性无进展生存率（mPFS）作为主要结局，mPFS 是总体生存率的外部证明替代指标。
方法
标准治疗（SOC）为雄激素剥夺治疗加或不加根治性前列腺放射治疗。SOC 共有 460 例，SOC 加多西他赛 230 例，随机分配 2:1。采用标准生存方法和意向治疗。使用调整后的 Cox 回归模型总结治疗效果估计，若非比例风险则转换为受限平均生存时间。mPFS（新发转移、骨骼相关事件或前列腺癌死亡）具有 70%的效力（α=0.05），风险比（HR）为 0.70。次要终点包括总生存率、无失败生存率（FFS）和无进展生存率（PFS：mPFS、局部区域进展）。
结果
中位随访时间为 6.5 年，SOC 出现 142 例 mPFS 事件（3 年和 54%的增加超过了之前的报告）。SOC 加多西他赛在 mPFS 上没有明显的优势（HR=0.89，95%置信区间[CI]为 0.66 至 1.19；P=0.43）；SOC 加多西他赛 5 年 mPFS 为 82%（95%CI=78%至 87%），SOC 为 77%（95%CI=73%至 81%）。次要结局显示，SOC 加多西他赛改善了 FFS（HR=0.70，95%CI=0.55 至 0.88；P=0.002）和 PFS（非比例 P=0.03，受限平均生存时间差异=5.8 个月，95%CI=0.5 至 11.2；P=0.03），但无总体生存获益的良好证据（SOC 死亡 125 例；HR=0.88，95%CI=0.64 至 1.21；P=0.44）。没有证据表明 SOC 加多西他赛增加晚期毒性：SOC 为 1 年后 29%，SOC 加多西他赛为 30%，3-5 级毒性。
结论
有强有力的证据表明，SOC 加多西他赛改善了 FFS 和 PFS（之前显示可增加质量调整生命年），且没有晚期毒性增加，这并未转化为长期结局的获益。这可能会影响个别病例的患者管理。
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