蔡奕波,谢 丽.如何选择初始不可切除的结直肠癌肝转移患者一线全身治疗策略:CAIRO5研究结果解读[J].肿瘤学杂志,2023,29(9):799-808. |
如何选择初始不可切除的结直肠癌肝转移患者一线全身治疗策略:CAIRO5研究结果解读 |
How to Choose the First-Line Systemic Treatment Strategies for Patients with Initially Unresectable Colorectal Cancer Liver Metastases: Interpretation of CAIRO5 Study Results |
投稿时间:2023-09-05 |
DOI:10.11735/j.issn.1671-170X.2023.09.B014 |
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中文关键词: 结直肠癌肝转移 肿瘤部位 RAS/BRAF基因突变 治疗策略 |
英文关键词:colorectal cancer liver metastasis tumor location RAS/BRAF gene mutation treatment strategies |
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中文摘要: |
摘 要:CAIRO5是一项开放标签、多中心、随机、对照Ⅲ期研究,旨在比较对于初始不可切除的结直肠癌肝转移(colorectal cancer liver metastases,CRLM)患者,目前临床常用的一线全身治疗策略的疗效及安全性。该研究在2014年11月13日至2022年1月31日期间在荷兰46个和比利时1个二/三级医疗中心进行。根据原发部位及基因状态进行分层随机分组,右侧原发性肿瘤部位或RAS或者BRAFV600E突变肿瘤患者随机分配(1∶1)接受FOLFOX或FOLFIRI联合贝伐单抗(A组)或者FOLFOXIRI联合贝伐单抗(B组)。左侧肿瘤且RAS和BRAFV600E野生型肿瘤患者随机分配(1∶1)接受FOLFOX或FOLFIRI联合贝伐单抗(C组)或者FOLFOX或FOLFIRI联合帕尼单抗(D组)。主要研究终点是ITT人群的无进展生存期。本研究共纳入530例初始不可切除的CRLM患者,其中A组148例(28%),B组146例(28%),C组118例(22%),D组118例(22%)。C组和D组因研究失败而提前关闭。右侧原发性肿瘤部位或者RAS或BRAFV600E突变肿瘤患者中,与FOLFOX或FOLFIRI加贝伐单抗治疗组相比较,FOLFOXIRI联合贝伐单抗治疗组可以延长中位无进展生存期(10.6个月vs 9.0 个月,P=0.032),降低CRLM患者的疾病进展或死亡风险23%。而在左侧肿瘤且RAS和BRAFV600E野生型肿瘤患者中,FOLFOX或FOLFIRI联合贝伐单抗治疗组和FOLFOX或FOLFIRI联合帕尼单抗治疗组之间中位无进展生存期无统计学差异(10.8个月vs 10.4个月,P=0.46)。在安全性方面,FOLFOXIRI联合贝伐单抗治疗组严重不良事件(≥3级)明显高于FOLFOX或FOLFIRI加贝伐单抗治疗组(52% vs 31%),其中最常见的是中性粒细胞减少症,同时FOLFOXIRI联合贝伐单抗治疗组报告了7例与治疗相关死亡病例,显著高于其他治疗组。在左侧肿瘤且RAS和BRAFV600E野生型肿瘤患者中,FOLFOX或FOLFIRI中加入帕尼单抗,相比较于贝伐单抗,并未显示临床获益,但与更高的严重不良事件(≥3级)发生率相关。CAIRO5研究结果提示,对于右半结肠或者RAS或BRAFV600E突变型初始不可切除CRLM患者,FOLFOXIRI联合贝伐单抗是首选治疗方案;而对于左半结肠RAS和BRAFV600E野生型患者,在FOLFOX或FOLFIRI的基础上联合帕尼单抗对比贝伐单抗并未能获得更好的临床疗效,且将增加治疗相关毒性。 |
英文摘要: |
Abstract: CAIRO-5 is an open-label, multi-center, randomized, controlled phase Ⅲ study designed to compare the efficacy and safety of currently most active first-line systemic treatment strategies in patients with initially unresectable colorectal cancer liver metastases (CRLM). The study was conducted in Dutch 46 and Belgian 1 secondary/tertiary centers between November 13, 2014 and January 31, 2022. Stratified randomization was performed according to the primary tumor site and gene status. Patients with right-sided primary tumor, or RAS or BRAFV600E mutated tumors were randomly assigned (1∶1) to receive FOLFOX or FOLFIRI plus bevacizumab (group A) or FOLFOXIRI plus bevacizumab (group B). Patients with left-sided and RAS and BRAFV600E wild-type tumors were randomly assigned (1∶1) to receive FOLFOX or FOLFIRI plus bevacizumab (group C) or FOLFOX or FOLFIRI plus panitumumab (group D). The primary outcome was progression-free survival in the intention-to-treat population. A total of 530 patients with initially unresectable CRLM were enrolled in this study, including 148 cases (28%) in group A, 146 cases (28%) in group B, 118 cases (22%) in group C, and 118 cases in group D (22%). Groups C and D were prematurely closed for futility. Among patients with right-sided primary tumor, or RAS or BRAFV600E mutated tumors, treatment with FOLFOXIRI plus bevacizumab prolonged median progression-free survival compared with FOLFOX or FOLFIRI plus bevacizumab (10.6 months vs 9.0 months, P=0.032), reducing the risk of disease progression or death in patients with CRLM by 23%. For patients with left-sided, and RAS and BRAFV600E wild-type tumors, there was no statistically significant difference in median progression-free survival between group C and group D (10.8 months vs 10.4 months,P=0.46). In terms of safety, the serious adverse events (grade ≥ 3) in group B were significantly higher than those in group A (52% vs 31% ). The most common grade 3~4 event was neutropenia. Remarkably, 7 treatment-related deaths were reported in group B, which was significantly higher than in the other treatment groups. In patients with left-sided, and RAS and BRAFV600E wild-type tumors, the addition of panitumumab to FOLFOX or FOLFIRI did not show clinical benefit compared with bevacizumab, but was associated with higher incidence of serious adverse events(≥grade 3). The results of the CAIRO5 study suggest that FOLFOXIRI combined with bevacizumab is the preferred treatment option for initial unresectable CRLM with right-sided primary tumor, or RAS or BRAFV600E mutated tumors. In patients with left-sided and RAS and BRAFV600E wild-type tumors, combining panitumumab on the basis of FOLFOX or FOLFIRI did not have a survival benefit than bevacizumab, while increasing treatment-related toxicity. |
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