BRAFV600E 突变型转移性结直肠癌患者一线 FOLFOXIRI 和贝伐珠单抗治疗的获益：原发肿瘤位置是否重要？
Benefit from upfront FOLFOXIRI and bevacizumab in BRAFV600E-mutated metastatic colorectal cancer patients: does primary tumour location matter?
机构信息
Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
Clinical & Translational Research, Medical Affairs, Caris Life Sciences, Phoenix, AZ, USA.
出版信息
Br J Cancer. 2022 Sep;127(5):957-967. doi: 10.1038/s41416-022-01852-0. Epub 2022 Jun 3.
BACKGROUND
Recent data suggest that BRAFV600E-mutated metastatic colorectal cancer (mCRC) patients with right-sided tumours and ECOG-PS = 0 may achieve benefit from the triplet regimen differently than those with left-sided tumours and ECOG-PS > 0.
METHODS
The predictive impact of primary sidedness and ECOG-PS was evaluated in a large real-life dataset of 296 BRAFV600E-mutated mCRC patients treated with upfront triplet or doublet ± bevacizumab. Biological differences between right- and left-sided BRAFV600E-mutated CRCs were further investigated in an independent cohort of 1162 samples.
RESULTS
A significant interaction effect between primary sidedness and treatment intensity was reported in terms of both PFS (p = 0.010) and OS (p = 0.003), with a beneficial effect of the triplet in the right-sided group and a possible detrimental effect in the left-sided. No interaction effect was observed between ECOG-PS and chemo-backbone. In the MSS/pMMR population, a consistent trend for a side-related subgroup effect was observed when FOLFOXIRI ± bevacizumab was compared to oxaliplatin-based doublets±bevacizumab (p = 0.097 and 0.16 for PFS and OS, respectively). Among MSS/pMMR tumours, the BM1 subtype was more prevalent in the right-sided group (p = 0.0019, q = 0.0139). No significant differences were observed according to sidedness in the MSI-H/dMMR population.
CONCLUSIONS
Real-life data support the use of FOLFOXIRI ± bevacizumab only in BRAFV600E-mutated mCRC patients with right-sided tumours.
背景
最近的数据表明，右侧肿瘤且 ECOG-PS=0 的 BRAFV600E 突变转移性结直肠癌（mCRC）患者与左侧肿瘤且 ECOG-PS>0 的患者相比，可能从三联方案中获益不同。
方法
在接受一线三联或双联±贝伐珠单抗治疗的 296 例 BRAFV600E 突变 mCRC 患者的大型真实世界数据集中，评估了原发侧和 ECOG-PS 的预测影响。在独立的 1162 例样本队列中进一步研究了右和左 BRAFV600E 突变 CRC 之间的生物学差异。
结果
报告了原发侧和治疗强度之间的显著交互作用，表现在 PFS（p=0.010）和 OS（p=0.003）方面，三联方案在右侧组中有益，而在左侧组中可能有害。ECOG-PS 和化疗方案之间没有观察到交互作用。在 MSS/pMMR 人群中，与奥沙利铂为基础的双联±贝伐珠单抗相比，FOLFOXIRI±贝伐珠单抗观察到一致的与侧相关亚组效应的趋势（pFS 和 OS 分别为 0.097 和 0.16）。在 MSS/pMMR 肿瘤中，BM1 亚型在右侧组更为常见（p=0.0019，q=0.0139）。在 MSI-H/dMMR 人群中，根据侧位未观察到显著差异。
结论
真实世界的数据支持仅在右侧肿瘤的 BRAFV600E 突变 mCRC 患者中使用 FOLFOXIRI±贝伐珠单抗。
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