| 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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