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RAS 野生型转移性结直肠癌患者一线 FOLFIRI 联合帕尼单抗治疗后,原发肿瘤位置和早期肿瘤退缩对结局的影响。

Impact of Primary Tumour Location and Early Tumour Shrinkage on Outcomes in Patients with RAS Wild-Type Metastatic Colorectal Cancer Following First-Line FOLFIRI Plus Panitumumab.

机构信息

Department of Oncology and Haematology, Klinikum Oldenburg, Oldenburg, Germany.

Department of Hematology and Oncology, Städtisches Klinikum München, Munich, Germany.

出版信息

Drugs R D. 2019 Sep;19(3):267-275. doi: 10.1007/s40268-019-0278-8.

Abstract

OBJECTIVE

Data from a trial of first-line panitumumab plus FOLFIRI (folinic acid, infusional 5-fluorouracil and irinotecan) in metastatic colorectal cancer were retrospectively analysed to investigate the effects of primary tumour location and early tumour shrinkage on outcomes.

METHODS

Patients with RAS wild-type metastatic colorectal cancer from a single-arm, open-label phase II study (NCT00508404) were included. Tumours located from the splenic flexure to rectum and in the caecum to transverse colon were defined as left- and right-sided, respectively. Baseline characteristics were summarised by primary tumour location and the effects of primary tumour location on outcomes-including objective response rate, resection rate, depth of response, duration of response and progression-free survival-were analysed. Progression-free survival and objective response rate were analysed by early tumour shrinkage status.

RESULTS

Primary tumour location was determined in 52/69 (75%) patients with RAS wild-type metastatic colorectal cancer; 45 (87%) had left-sided disease. Median progression-free survival was longer in patients with left-sided tumours (11.2 vs. 7.2 months for right-sided disease) and more of these patients experienced early tumour shrinkage ≥ 30% (53% vs. 29%). Early tumour shrinkage ≥ 30% was associated with improved progression-free survival irrespective of tumour location. More patients with early tumour shrinkage ≥ 30% achieved a partial or complete response. Objective response rate, duration of response, depth of response and resection rates were similar in patients with left- and right-sided tumours.

CONCLUSIONS

This analysis has confirmed a prognostic effect of primary tumour location in patients with RAS wild-type metastatic colorectal cancer receiving first-line panitumumab plus FOLFIRI. Early tumour shrinkage was associated with improved progression-free survival irrespective of tumour location. In right-sided disease, early tumour shrinkage may identify a subgroup of patients who might respond to panitumumab. CLINICALTRIALS.

GOV IDENTIFIER

NCT00508404.

摘要

目的

对一线帕尼单抗联合 FOLFIRI(亚叶酸、持续输注氟尿嘧啶和伊立替康)治疗转移性结直肠癌的临床试验数据进行回顾性分析,以探讨原发肿瘤位置和早期肿瘤退缩对结局的影响。

方法

纳入来自一项单臂、开放标签的 II 期研究(NCT00508404)的 RAS 野生型转移性结直肠癌患者。肿瘤位于脾曲至直肠和盲肠至横结肠之间的定义为左侧和右侧。根据原发肿瘤位置总结基线特征,并分析原发肿瘤位置对结局的影响,包括客观缓解率、切除率、缓解深度、缓解持续时间和无进展生存期。根据早期肿瘤退缩情况分析无进展生存期和客观缓解率。

结果

52/69(75%)例 RAS 野生型转移性结直肠癌患者确定了原发肿瘤位置;45 例(87%)为左侧肿瘤。左侧肿瘤患者的中位无进展生存期较长(11.2 个月 vs. 右侧疾病的 7.2 个月),且更多患者出现早期肿瘤退缩≥30%(53% vs. 29%)。无论肿瘤位置如何,早期肿瘤退缩≥30%均与无进展生存期的改善相关。更多早期肿瘤退缩≥30%的患者获得部分或完全缓解。左侧和右侧肿瘤患者的客观缓解率、缓解持续时间、缓解深度和切除率相似。

结论

本分析证实了 RAS 野生型转移性结直肠癌患者接受一线帕尼单抗联合 FOLFIRI 治疗时原发肿瘤位置的预后影响。早期肿瘤退缩与无进展生存期的改善相关,与肿瘤位置无关。在右侧疾病中,早期肿瘤退缩可能可以识别出可能对帕尼单抗有反应的患者亚组。临床试验.gov 标识符:NCT00508404。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b77/6738356/b9d2db06ac36/40268_2019_278_Fig1_HTML.jpg

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