Early Decline in Cancer Antigen 125 as a Surrogate for Progression-Free Survival in Recurrent Ovarian Cancer
Early Decline in Cancer Antigen 125 as a Surrogate for Progression-Free Survival in Recurrent Ovarian Cancer
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DOI：
10.1093/jnci/djr282
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发表时间：
2011-09-01
期刊：
影响因子：
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通讯作者：
Simes, R. John
中科院分区：
文献类型：
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作者：
Lee, Chee K.;Friedlander, Michael;Simes, R. John
我们使用了2005年4月至2007年9月期间招募的铂敏感卵巢患者CAELYX（CALYPSO）试验中886例患者的数据，研究癌抗原125（CA 125）早期下降和早期肿瘤缓解作为预后因素的作用，以及卡铂-聚乙二醇化脂质体多柔比星（CPLD）治疗优于卡铂-紫杉醇（CP）治疗的替代因素在一次具有里程碑意义的分析中。通过Kaplan-Meier分析估计无进展生存期（PFS）。我们使用单变量和多变量考克斯比例风险分析来评估早期下降和早期反应作为与CP相比的CPLD治疗益处的替代物。所有统计检验均为双侧检验。早期下降（定义为CA 125每月下降至少50%）与PFS改善相关（调整后的进展风险比[HR]= 0.81，95%置信区间[CI] = 0.67至0.97，P = 0.02），但早期缓解（完全或部分缓解）与PFS改善无关。与CP相比，CPLD与PFS改善相关（HR = 0. 82，95% CI = 0. 69至0. 96，P = 0. 01）。然而，与CP患者相比，更少的CPLD患者有早期下降（161 [37.4%] vs 233 [51.2%]，P <0.001）或早期反应（146 [33.9%] vs 176 [38.7%]，P = 0.14）。校正早期下降后，CPLD患者的PFS无统计学显著变化（校正HR = 0.80，95% CI = 0.68 - 0.94，P = 0.007）。这些发现与预期相反，如果这些标志物是治疗获益的良好替代品。
We used data from 886 patients from the CAELYX in Platinum Sensitive Ovarian Patients (CALYPSO) trial, recruited between April 2005 and September 2007, to examine the role of early decline in cancer antigen 125 (CA125) and early tumor response as prognostic factors and surrogates for superiority of treatment with carboplatin-pegylated liposomal doxorubicin (CPLD) compared with carboplatin-paclitaxel (CP) in a landmark analysis. Progression-free survival (PFS) was estimated by Kaplan-Meier analyses. We used univariate and multivariable Cox proportional hazards analyses to assess early decline and early response as surrogates for CPLD treatment benefit compared with CP. All statistical tests were two-sided. Early decline (defined as rate of CA125 decrease of at least 50% per month) was associated with improved PFS (adjusted hazard ratio [HR] for progression = 0.81, 95% confidence interval [CI] = 0.67 to 0.97, P = .02) but early response (complete or partial responses) was not. CPLD was associated with improved PFS compared with CP (HR = 0.82, 95% CI = 0.69 to 0.96, P = .01). However, fewer CPLD patients had an early decline (161 [37.4%] vs 233 [51.2%], P < .001) or an early response (146 [33.9%] vs 176 [38.7%], P = .14) compared with CP patients. The PFS for CPLD patients did not change statistically significantly after adjustment for early decline (adjusted HR = 0.80, 95% CI = 0.68 to 0.94, P = .007). These findings are opposite to what would be expected if these markers were good surrogates for treatment benefit.