A randomised study of encorafenib, cetuximab, and FOLFIRI versus FOLFIRI with or without bevacizumab in BRAF V600E-mutant colorectal cancer: BREAKWATER Cohort 3.

patients_and_methods

In BREAKWATER Cohort 3, eligible patients with previously untreated BRAF V600E-mutant mCRC were randomly assigned 1:1 to receive EC+FOLFIRI or FOLFIRI with or without bevacizumab (control).

在 BREAKWATER 队列 3 中，符合条件的先前未经治疗的 BRAF V600E 突变 mCRC 患者被随机分配为 1:1 接受 EC+FOLFIRI 或 FOLFIRI，有或没有贝伐单抗 (对照组)。

The primary endpoint was objective response rate(ORR) by blinded independent central review (BICR), and the key secondary endpoint was progression-free survival(PFS) by BICR.

主要终点是通过盲法独立中心评审（BICR）评估的客观缓解率（ORR），关键次要终点是通过BICR评估的无进展生存（PFS）

Other secondary endpoints included overall survival(OS) and safety.

其他次要终点包括总生存（OS）和安全性

Results

A total of 147 patients were randomly allocated in Cohort 3 (EC+FOLFIRI, n = 73; control, n = 74) with similar baseline demographics and disease characteristics across arms.

在第三队列中，共有147名患者被随机分配（EC+FOLFIRI组，n=73；对照组，n=74），两组患者的基线人口统计学特征和疾病特征相似。

EC+FOLFIRI demonstrated clinically meaningful and statistically significant improvement in ORR by BICR {64.4% versus 39.2%, odds ratio = 2.756 [95% confidence interval(CI) 1.420-5.348], one-sided P-value = 0.0011}, meeting the primary endpoint (1 March 2025, data cutoff).

EC+FOLFIRI通过BICR显示出临床意义和统计学上显著的客观缓解率(ORR)改善（64.4%对比39.2%，优势比=2.756 [95%置信区间(CI) 1.420-5.348]，单侧P值=0.0011），满足主要终点（2025年3月1日，数据截止）。

At the 6 January 2026 data cutoff, the key secondary endpoint was met, with EC+FOLFIRI demonstrating a clinically meaningful and statistically significant PFS [hazard ratio= 0.44 (95% CI 0.27-0.70), one-sided P-value = 0.0002, 15.2 versus 8.3 months].

截至2026年1月6日的数据截止日期，主要次要终点已达成，EC+FOLFIRI显示出具有临床意义且统计学上显著的无进展生存期（PFS）[风险比=0.44（95%置信区间0.27-0.70），单侧P值=0.0002，15.2个月对比8.3个月]。

Prolonged OS was also observed with EC+FOLFIRI (hazard ratio= 0.56 [95% CI 0.34-0.94], not estimable versus 20.3 months).

使用EC+FOLFIRI也观察到总生存期（OS）延长（风险比=0.56 [95%置信区间0.34-0.94]，无法估计对比20.3个月）。

Serious adverse eventrates were 49.3% versus 44.1% for the EC+FOLFIRI versus control arms, respectively.

严重不良事件的发生率在EC+FOLFIRI组和对照组中分别为49.3%和44.1%。

The safety profile was consistent with that known for each agent.

安全性特征与每种药物已知的特性一致。

Conclusions

EC+FOLFIRI demonstrated clinically meaningful and statistically significant improvements in ORR and PFS, with prolonged OS versus control in BRAF V600E-mutant mCRC.

EC+FOLFIRI 在 BRAF V600E 突变的转移性结直肠癌（mCRC）中显示出临床意义和统计学显著性的客观缓解率（ORR）和无进展生存期（PFS）改善，并且总生存期（OS）延长，与对照组相比具有优势。

The safety profile was generally manageable, with no new safety signals.

安全性方面总体上是可管理的，没有出现新的安全信号。

These data support EC+FOLFIRI as an additional new standard of care for patients with BRAF V600E-mutant mCRC, enabling treatment personalisation.

这些数据支持将EC+FOLFIRI作为BRAF V600E突变型转移性结直肠癌患者的另一种新的治疗标准，使治疗个性化成为可能。