Early tumor shrinkage and depth of response predict long-term outcome in metastatic colorectal cancer patients treated with first-line chemotherapy plus bevacizumab: results from phase III TRIBE trial by the Gruppo Oncologico del Nord Ovest
Early tumor shrinkage and depth of response predict long-term outcome in metastatic colorectal cancer patients treated with first-line chemotherapy plus bevacizumab: results from phase III TRIBE trial by the Gruppo Oncologico del Nord Ovest
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DOI：
10.1093/annonc/mdv112
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发表时间：
2015-06-01
影响因子：
50.5
通讯作者：
Falcone, A.
中科院分区：
文献类型：
--
作者：
Cremolini, C.;Loupakis, F.;Falcone, A.
背景：在转移性结直肠癌(MCRC)化疗+/-抗EGFR单抗(MCRC)一线试验中，早期肿瘤缩小(ETS)和反应深度(DOR)预测总生存率(OS)。在FOLFOXIRI加贝伐单抗(BEV)与FOLFIRI加BEV的III期部落试验中，研究了这些相关性和生存参数反应测量的预测准确性。患者和方法：采用里程碑式的方法定义可评估的人群。比较两组患者RECIST反应率、ETS和DOR的分布。通过单因素和多因素COX模型检验反应测量与无进展生存期(PFS)、进展后生存期(PPS)和OS的相关性。结果：FOLFOXIRI加BEV组患者Ets>；=20%的比例显著高于对照组(62.7%vs51.9%，P=0.025)。三胞胎+BEV组的DOR也显著高于对照组(43.4%vs37.8%，P=0.003)。在单变量分析和对其他预后变量进行分层的多变量模型中，ETS和DOR都与PFS、PPS和OS相关。结论：与FOLFIRI加BEV相比，FOLFOXIRI加BEV可改善ETS和DOR。在接受一线化疗加BEV治疗的患者中，实现快速和深度的肿瘤缩小持续延缓肿瘤进展和延长生存期。ETS是临床试验设计的一个有希望和有价值的终点，值得进一步研究。
Background: Early tumor shrinkage (ETS) and depth of response (DoR) predict overall survival (OS) in first-line trials of chemotherapy +/- anti-EGFR monoclonal antibodies in metastatic colorectal cancer (mCRC). These associations and the predictive accuracy of response measurements for survival parameters were investigated in the phase III TRIBE trial of FOLFOXIRI plus bevacizumab (bev) versus FOLFIRI plus bev.Patients and methods: A landmark approach was adopted to define the assessable population. The distribution of RECIST response rate, ETS and DoR was compared in the two arms. Associations between response measurements and progression-free survival (PFS), post-progression survival (PPS) and OS were tested by univariate and multivariate Cox models. Prediction performance of each factor was estimated by C-index.Results: A significantly higher percentage of patients in the FOLFOXIRI plus bev arm achieved ETS >= 20%, when compared with the control arm (62.7% versus 51.9%, P = 0.025). Also the DoR was significantly higher in the triplet plus bev arm (43.4% versus 37.8%, P = 0.003). Both ETS and DoR were associated with PFS, PPS and OS at the univariate analyses and in the multivariate models stratified for other prognostic variables. Both ETS and DoR were able to predict survival as accurately as RECIST response.Conclusion: FOLFOXIRI plus bev improves ETS and DoR when compared with FOLFIRI plus bev. Achieving rapid and deep tumor shrinkage consistently delays tumor progression and prolongs survival in patients treated with first-line chemotherapy plus bev. ETS is a promising and valuable end point for clinical trials' design deserving further investigation.