First-Line Systemic Treatment for Initially Unresectable Colorectal Liver Metastases: Post Hoc Analysis of the CAIRO5 Randomized Clinical Trial.

FOLFOX/FOLFIRI-panitumumab vs FOLFOX/FOLFIRI-bevacizumab increased response at the cost of more toxic effects in RAS/BRAFV600E wild-type, left-sided tumors.

在RAS/BRAFV600E野生型、左侧肿瘤患者中，FOLFOX/FOLFIRI-帕尼单抗与FOLFOX/FOLFIRI-贝伐单抗相比，提高了反应率，但代价是增加了更多的毒性效应。

Background

To present long-term outcomes of treatment with FOLFOXIRI plus bevacizumab vs FOLFOX/FOLFIRI plus bevacizumab and FOLFOX/FOLFIRI plus panitumumab vs FOLFOX/FOLFIRI + bevacizumab.

介绍使用FOLFOXIRI加贝伐单抗与FOLFOX/FOLFIRI加贝伐单抗以及FOLFOX/FOLFIRI加帕尼单抗与FOLFOX/FOLFIRI加贝伐单抗治疗的长期结果。

DESIGN, SETTING, AND PARTICIPANTS: The randomized phase 3 CAIRO5 trial included patients with initially unresectable CRLM in 46 Dutch centers and 1 Belgian center between November 2014 and January 2022.

设计、设置和参与者：随机III期CAIRO5试验在2014年11月至2022年1月期间，纳入了46个荷兰中心和1个比利时中心的最初不可切除的CRLM患者。

A liver expert panel repeatedly evaluated resectability.

一个肝脏专家小组反复评估了可切除性。

intervention

Patients with RAS/BRAFV600E-variant and/or right-sided tumors randomly received FOLFOX/FOLFIRI-bevacizumab (group 1) or FOLFOXIRI-bevacizumab (group 2), and those with RAS/BRAFV600E wild-type, left-sided tumors received FOLFOX/FOLFIRI-bevacizumab (group 3) or FOLFOX/FOLFIRI-panitumumab (group 4).

携带RAS/BRAFV600E变异和/或右侧肿瘤的患者随机接受FOLFOX/FOLFIRI-贝伐单抗（第1组）或FOLFOXIRI-贝伐单抗（第2组），而携带RAS/BRAFV600E野生型、左侧肿瘤的患者接受FOLFOX/FOLFIRI-贝伐单抗（第3组）或FOLFOX/FOLFIRI-帕尼单抗（第4组）。

Adjuvant chemotherapy (ACT) after complete local treatment was recommended but not standard.

在完全局部治疗后推荐进行辅助化疗（ACT），但并非标准做法。

main_outcomes_and_measures

Overall survival(OS) was analyzed as a secondary outcome.

总生存（OS）被分析为次要结果。

Other outcomes were post hoc analyses.

其他结果是事后分析。

Results

A total of 530 patients (327 male [62%] and 203 female individuals [38%]; median age, 62 [IQR, 54-69] years) were randomized: 148 in group 1, 146 in group 2, 118 in group 3, and 118 in group 4.

共有530名患者（男性327名[62%]，女性203名[38%]；中位年龄62岁[四分位数间距，54-69岁]）被随机分配：148名在第1组，146名在第2组，118名在第3组，以及118名在第4组。

The median OS in group 1 was 23.6 (95% CI, 20.1-27.5) vs 24.1 (95% CI, 21.0-30.9) months in group 2 (hazard ratio[HR], 0.90; 95% CI, 0.70-1.17; P = .44), and 39.9 (95% CI, 30.7-44.6) in group 3 vs 38.3 (95% CI, 35.3-51.3) months in group 4 (HR, 0.95; 95% CI, 0.68-1.32; P = .75).

第1组的中位总生存期为23.6个月（95%置信区间，20.1-27.5），而第2组为24.1个月（95%置信区间，21.0-30.9）（风险比[HR]，0.90；95%置信区间，0.70-1.17；P = .44），第3组为39.9个月（95%置信区间，30.7-44.6），第4组为38.3个月（95%置信区间，35.3-51.3）（HR，0.95；95%置信区间，0.68-1.32；P = .75）。

OS was longest after complete local treatment without early (≤6 months) recurrence (64.3 months; 95% CI, 57.6 to not reached) and salvage local treatment options after early recurrence (58.9; 95% CI, 47.3 to not reached), followed by patients without salvage local treatment after early recurrence (30.5; 95% CI, 24.4-33.4) and with incomplete local treatment (28.7; 95% CI, 25.9-38.3), and worst in patients with continued unresectability (18.3; 95% CI, 15.7-20.0).

在没有早期（≤6个月）复发的完全局部治疗后，总生存期最长（64.3个月；95%置信区间，57.6至未达到），其次是早期复发后的挽救性局部治疗选择（58.9个月；95%置信区间，47.3至未达到），然后是没有早期复发后挽救性局部治疗的患者（30.5个月；95%置信区间，24.4-33.4）和局部治疗不完全的患者（28.7个月；95%置信区间，25.9-38.3），在持续无法切除的患者中总生存期最差（18.3个月；95%置信区间，15.7-20.0）。

After confounder adjustment, ACT was associated with longer OS (HR, 0.66; 95% CI, 0.44-0.98) and relapse-free survival (HR, 0.65; 95% CI, 0.48-0.88) and less early recurrence without salvage local treatment (odds ratio, 0.46; 95% CI, 0.25-0.85).

在校正混杂因素后，ACT与更长的总生存期（HR, 0.66; 95% 置信区间, 0.44-0.98）和无复发生存期（HR, 0.65; 95% 置信区间, 0.48-0.88）相关，且在没有挽救性局部治疗的情况下早期复发较少（比值比, 0.46; 95% 置信区间, 0.25-0.85）。

conclusions_and_relevance

These results support using FOLFOX/FOLFIRI-bevacizumab for patients with initially unresectable CRLM irrespective of RAS/BRAFV600E status and tumor sidedness.

这些结果支持无论RAS/BRAFV600E状态和肿瘤侧别如何，都对初始不可切除的CRLM患者使用FOLFOX/FOLFIRI-贝伐单抗治疗。

Patients with complete local liver treatment with salvage local treatment in case of early recurrence had the longest OS.

对于早期复发时接受挽救性局部治疗的完全局部肝脏治疗患者，其总生存期最长。

ACT might be considered for these patients.

这些患者可能会考虑接受ACT治疗。

trial_registration

ClinicalTrials.gov NCT02162563.

ClinicalTrials.gov 注册号 NCT02162563。