恩考芬尼联合西妥昔单抗作为治疗后 V600E 突变转移性结直肠癌的新标准：BEACON 研究的更新生存结果和亚组分析。
Encorafenib Plus Cetuximab as a New Standard of Care for Previously Treated V600E-Mutant Metastatic Colorectal Cancer: Updated Survival Results and Subgroup Analyses from the BEACON Study.
机构信息
Vall d'Hebron University Hospital (HUVH), Vall d'Hebron Institute of Oncology (VHIO), UVic-UCC, IOB-Quiron, Barcelona, Spain.
West Cancer Center, OneOncology, Germantown, TN.
出版信息
J Clin Oncol. 2021 Feb 1;39(4):273-284. doi: 10.1200/JCO.20.02088.
PURPOSE
BEACON CRC evaluated encorafenib plus cetuximab with or without binimetinib versus investigators' choice of irinotecan or FOLFIRI plus cetuximab in patients with V600E-mutant metastatic colorectal cancer (mCRC), after progression on 1-2 prior regimens. In the previously reported primary analysis, encorafenib, binimetinib plus cetuximab (ENCO/BINI/CETUX; triplet) and encorafenib plus cetuximab (ENCO/CETUX; doublet) regimens improved overall survival (OS) and objective response rate (ORR; by blinded central review) versus standard of care. The purpose of this analysis was to report updated efficacy and safety data.
METHODS
In this open-label, phase III trial, 665 patients with V600E-mutant mCRC were randomly assigned 1:1:1 to receive triplet, doublet, or control. Primary end points were OS and independently reviewed ORR comparing triplet to control. OS for doublet versus control was a key secondary end point. Updated analyses include 6 months of additional follow-up and ORR for all randomized patients.
RESULTS
Patients received triplet (n = 224), doublet (n = 220), or control (n = 221). Median OS was 9.3 months (95% CI, 8.2 to 10.8) for triplet and 5.9 months (95% CI, 5.1 to 7.1) for control (hazard ratio [HR], 0.60 [95% CI, 0.47 to 0.75]). Median OS for doublet was 9.3 months (95% CI, 8.0 to 11.3) (HR control, 0.61 [95% CI, 0.48 to 0.77]). Confirmed ORR was 26.8% (95% CI, 21.1% to 33.1%) for triplet, 19.5% (95% CI, 14.5% to 25.4%) for doublet, and 1.8% (95% CI, 0.5% to 4.6%) for control. Adverse events were consistent with the prior primary analysis, with grade ≥ 3 adverse events in 65.8%, 57.4%, and 64.2% for triplet, doublet, and control, respectively.
CONCLUSION
In the BEACON CRC study, encorafenib plus cetuximab improved OS, ORR, and progression-free survival in previously treated patients in the metastatic setting compared with standard chemotherapy. Based on the primary and updated analyses, encorafenib plus cetuximab is a new standard care regimen for previously treated patients with V600E mCRC.
目的
BEACON CRC 评估了 encorafenib 联合 cetuximab 与 binimetinib 或不与 binimetinib 联合，与 irinotecan 或 FOLFIRI 联合 cetuximab 相比，用于治疗 V600E 突变型转移性结直肠癌（mCRC）患者，这些患者在一线或二线治疗方案进展后接受治疗。在之前报道的主要分析中，encorafenib、binimetinib 联合 cetuximab（ENCO/BINI/CETUX；三联）和 encorafenib 联合 cetuximab（ENCO/CETUX；双联）方案改善了总生存期（OS）和客观缓解率（ORR；由盲法中心审查）与标准护理相比。本分析的目的是报告更新的疗效和安全性数据。
方法
在这项开放标签、III 期试验中，665 例 V600E 突变型 mCRC 患者以 1:1:1 的比例随机分配接受三联、双联或对照组治疗。主要终点是 OS，并通过独立的中心审查比较三联与对照组的 ORR。与对照组相比，双联的 OS 是一个关键次要终点。更新分析包括 6 个月的额外随访和所有随机患者的 ORR。
结果
患者接受三联（n=224）、双联（n=220）或对照组（n=221）治疗。三联的中位 OS 为 9.3 个月（95%CI，8.2 至 10.8），对照组为 5.9 个月（95%CI，5.1 至 7.1）（HR，0.60 [95%CI，0.47 至 0.75]）。双联的中位 OS 为 9.3 个月（95%CI，8.0 至 11.3）（HR 对照组，0.61 [95%CI，0.48 至 0.77]）。三联的确认 ORR 为 26.8%（95%CI，21.1%至 33.1%），双联为 19.5%（95%CI，14.5%至 25.4%），对照组为 1.8%（95%CI，0.5%至 4.6%）。不良事件与之前的主要分析一致，三联、双联和对照组的≥3 级不良事件发生率分别为 65.8%、57.4%和 64.2%。
结论
在 BEACON CRC 研究中，encorafenib 联合 cetuximab 与标准化疗相比，改善了转移性疾病中既往治疗患者的 OS、ORR 和无进展生存期。基于主要和更新的分析，encorafenib 联合 cetuximab 是治疗 V600E 突变型 mCRC 患者的新的标准治疗方案。
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