Burden of Metastatic Castrate Naive Prostate Cancer Patients, to Identify Men More Likely to Benefit from Early Docetaxel: Further Analyses of CHAARTED and GETUG-AFU15 Studies.
Burden of Metastatic Castrate Naive Prostate Cancer Patients, to Identify Men More Likely to Benefit from Early Docetaxel: Further Analyses of CHAARTED and GETUG-AFU15 Studies.
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DOI：
10.1016/j.eururo.2018.02.001
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发表时间：
2018-06
期刊：
影响因子：
23.4
通讯作者：
Sweeney C
中科院分区：
文献类型：
--
作者：
Gravis G;Boher JM;Chen YH;Liu G;Fizazi K;Carducci MA;Oudard S;Joly F;Jarrard DM;Soulie M;Eisenberger MJ;Habibian M;Dreicer R;Garcia JA;Hussain MHM;Kohli M;Vogelzang NJ;Picus J;DiPaola R;Sweeney C
多西紫杉醇(D)在开始雄激素剥夺疗法(ADT)治疗转移性去势幼稚前列腺癌(ADT)时，显示出对高容量(HV)疾病患者的明显生存益处。目前尚不清楚低容量(LV)疾病的患者是否受益于早期的D.确定CHAARTED和GETUG-AFU15研究中患者亚组的总体数据的总体存活率(OS)，这些数据由转移负担(HV和LV)和转移发生的时间(诊断时或先前的局部治疗后[PRLT])定义。数据来自ADT单独或ADT+D-GETUG-AFU15(N=385)和CHAARTED(N=790)两个独立的III期试验，生存者的中位随访时间分别为83.2和48.2个月。统一了HV和LV病的定义。主要的终点是操作系统。汇总数据的Meta分析结果显示，HV和LV亚组之间的ADT+D和ADT效应大小存在显著的异质性(p=0.017)，但未能检测到前组和PRLT亚组之间的ADT+D和ADT效应大小的异质性(p=0.40)。在HV病患者中加D对改善中位OS的效果一致(HV-ADT分别为34.4mo和35.1mo，HV-adt+D分别为51.2mo和39.8mo；合并平均危险比或HR(95%可信区间[CI])0.68([95%CI0.56；0.82]，p<；0.001)。在CHAARTED和GETUG-AFU15中，LV-ADT+D和NR分别为63.5和63.5；合并HR(95%CI)为1.03(95%CI为0.77；1.38)。汇总数据显示，无论患者是否有PRLT，LV和HV亚组中早期D的异质性都没有证据。后组分组分析基于两个独立的III期随机试验的汇总数据。在CHAARTED和GETUG-AFU15研究中，使用D治疗LV没有明显的生存益处。在这两项研究中，早期D在HV患者中显示出一致的效果和改善的OS。开始雄激素剥夺治疗(ADT)的转移性前列腺癌负担较高的患者预后较差，更有可能从早期多西紫杉醇中受益。单用ADT的小剂量患者总体生存时间更长，多西紫杉醇的毒性可能大于其益处。
Docetaxel (D) at the time of starting androgen deprivation therapy (ADT) for metastatic castrate naive prostate cancer shows a clear survival benefit for patients with high-volume (HV) disease. It is unclear whether patients with low-volume (LV) disease benefit from early D. To define the overall survival (OS) of aggregate data of patient subgroups from the CHAARTED and GETUG-AFU15 studies, defined by metastatic burden (HV and LV) and time of metastasis occurrence (at diagnosis or after prior local treatment [PRLT]). Data were accessed from two independent phase III trials of ADT alone or ADT + D—GETUG-AFU15 (N = 385) and CHAARTED (N = 790), with median follow-ups for survivors of 83.2 and 48.2 mo, respectively. The definition of HV and LV disease was harmonized. The primary end point was OS. Meta-analysis results of the aggregate data showed significant heterogeneity in ADT + D versus ADT effect sizes between HV and LV subgroups (p = 0.017), and failed to detect heterogeneity in ADT + D versus ADT effect sizes between upfront and PRLT subgroups (p = 0.4). Adding D in patients with HV disease has a consistent effect in improving median OS (HV-ADT: 34.4 and 35.1 mo, HV-ADT + D: 51.2 and 39.8 mo in CHAARTED and GETUG-AFU15, respectively; pooled average hazard ratio or HR (95% confidence interval [CI]) 0.68 ([95% CI 0.56; 0.82], p < 0.001). Patients with LV disease showed much longer OS, without evidence that D improved OS (LV-ADT: not reached [NR] and 83.4; LV-ADT + D: 63.5 and NR in CHAARTED and GETUG-AFU15, respectively; pooled HR (95% CI) 1.03 (95% CI 0.77; 1.38). Aggregate data showed no evidence of heterogeneity of early D in LV and HV subgroups irrespective of whether patients had PRLT or not. Post hoc subgroup analysis was based on aggregated data from two independent phase III randomized trials. There was no apparent survival benefit in the CHAARTED and GETUG-AFU15 studies with D for LV. Across both studies, early D showed consistent effect and improved OS in HV patients. Patients with a higher burden of metastatic prostate cancer starting androgen deprivation therapy (ADT) have a poorer prognosis and are more likely to benefit from early docetaxel. Low-volume patients have longer overall survival with ADT alone, and the toxicity of docetaxel may outweigh its benefits.
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DOI：
10.1056/nejmoa1503747
发表时间：
2015-08-20
期刊：
The New England journal of medicine
影响因子：
--
作者：
Sweeney CJ;Chen YH;Carducci M;Liu G;Jarrard DF;Eisenberger M;Wong YN;Hahn N;Kohli M;Cooney MM;Dreicer R;Vogelzang NJ;Picus J;Shevrin D;Hussain M;Garcia JA;DiPaola RS
通讯作者：
DiPaola RS
影响因子：
8.4
作者：
Gravis, Gwenaelle;Marino, Patricia;Fizazi, Karim
通讯作者：
Fizazi, Karim
影响因子：
254.7
作者：
Siegel, Rebecca;Ma, Jiemin;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
影响因子：
51.1
作者：
Ryan, Charles J.;Smith, Matthew R.;Rathkopf, Dana E.
通讯作者：
Rathkopf, Dana E.
影响因子：
158.5
作者：
Scher, Howard I.;Fizazi, Karim;de Bono, Johann S.
通讯作者：
de Bono, Johann S.