Background

Doublets plus antiepidermal growth factor receptors monoclonal antibodies (EGFRi) are widely considered the preferable first-line regimen in patients with left-sided RAS/BRAF wild-type metastatic colorectal cancer (mCRC), resulting superior in terms of activity and efficacy compared to doublets plus bevacizumab. However, data comparing doublet plus EGFRi and triplet plus bevacizumab are lacking, and the relative benefit of an intensive regimen plus an antiangiogenic backbone in this population is debated.

Methods

This multicenter, retrospective study aimed at evaluating clinicians’ attitude to triplet-bevacizumab and doublet-EGFRi as first-line regimen in patients with left-sided RAS/BRAF wild-type mCRC treated in clinical practice at 22 Oncology Units from March 2012 to October 2020. A random case-control matching was performed to compare activity (ORR), and effectiveness (PFS, OS, secondary resection rate of metastases with curative intent) between triplet-bevacizumab and doublet-EGFRi, on the basis of ECOG-PS, age, gender, and burden of disease.

Results

A total of 718 patients were consecutively treated with doublet-EGFRi (686, 95.5%) or triplet-bevacizumab (32, 4.5%). After case-control matching, median PFS was 13.6 (95% CI, 8.9-31.7) and 16.1 (95% CI, 12.1-36.8) months (P= .621), while median OS was 30.2 (95% CI, 14.4-69.5) and 38.1 (95% CI, 33.1-101.1) months (P= .0283) in the doublet-EGFRi and the triplet-bevacizumab cohort, respectively. The ORR was 65.6% and 90.6% (P= .016), while the secondary resection rate was 18.8% and 46.9% (P= .016), in the doublet-EGFRi and the triplet-bevacizumab cohort, respectively. Triplet-bevacizumab was associated with a higher incidence of G3/G4 neutropenia (25.0% vs. 12.5%, P= .041).

Conclusion

Although a doublet-EGFRi remains the recommended upfront regimen in patients with left-sided RAS and BRAF wild-type mCRC, our real life data suggest a triplet-bevacizumab might be at least equally active and effective in properly selected cases.

中文翻译：

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临床医生对双联联合抗 EGFR 与三联联合贝伐单抗作为左侧 RAS 和 BRAF 野生型转移性结直肠癌患者一线治疗的态度：一项多中心、“真实”、病例对照研究

背景

双药联合抗表皮生长因子受体单克隆抗体 (EGFRi) 被广泛认为是左侧RAS/BRAF野生型转移性结直肠癌 (mCRC) 患者的首选一线治疗方案，与双药相比，在活性和疗效方面更优加贝伐单抗。然而，缺乏比较双药加 EGFRi 和三药加贝伐单抗的数据，并且在该人群中强化方案加抗血管生成骨干的相对益处存在争议。

方法

这项多中心、回顾性研究旨在评估临床医生对三联贝伐单抗和双联 EGFRi 作为 2012 年 3 月至 10 月在 22 个肿瘤科临床实践中治疗的左侧RAS/BRAF野生型 mCRC患者的一线方案的态度2020. 在 ECOG-PS 的基础上，进行随机病例对照匹配以比较三联贝伐单抗和双联 EGFRi 的活性 (ORR) 和有效性（PFS、OS、具有治愈意图的转移灶的二次切除率），年龄、性别和疾病负担。

结果

共有 718 名患者连续接受双药-EGFRi (686, 95.5%) 或三药-贝伐单抗 (32, 4.5%) 治疗。病例对照匹配后，中位 PFS 为 13.6（95% CI，8.9-31.7）和 16.1（95% CI，12.1-36.8）个月（P = .621），中位 OS 为 30.2（95% CI，14.4-在双联-EGFRi 和三联-贝伐单抗队列中分别为69.5) 和 38.1 (95% CI, 33.1-101.1) 个月 ( P = .0283)。在双联-EGFRi 和三联-贝伐单抗队列中，ORR 分别为 65.6% 和 90.6% ( P = .016)，而二次切除率分别为 18.8% 和 46.9% ( P = .016)。三联体贝伐单抗与更高的 G3/G4 中性粒细胞减少症发生率相关（25.0% 对 12.5%，P = .041）。

结论

Although a doublet-EGFRi remains the recommended upfront regimen in patients with left-sided RAS and BRAF wild-type mCRC, our real life data suggest a triplet-bevacizumab might be at least equally active and effective in properly selected cases.