抗 EGFR mAbs 是否应在未经治疗的右侧转移性结直肠癌的转化手术中停用？系统评价和荟萃分析。

Should anti-EGFR mAbs be discontinued for conversion surgery in untreated right-sided metastatic colorectal cancer? A systematic review and meta-analysis.

机构信息

Department of Oncology, Haimen People's Hospital, Haimen, China.

Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China.

出版信息

World J Surg Oncol. 2018 Oct 8;16(1):200. doi: 10.1186/s12957-018-1502-7.

DOI:10.1186/s12957-018-1502-7

PMID:30296945

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6176519/

Abstract

BACKGROUND

Previous studies have demonstrated that left-sided tumors have better prognoses than right-sided tumors in RAS wild-type mCRC (metastatic colorectal cancer) patients, while anti-EGFR mAbs appear to have no advantage compared with bevacizumab for right-sided tumors in these patients. Nevertheless, it remains unclear whether primary tumor location affects patients' options for potentially curative resection.

METHODS

PubMed, the Cochrane Library, Embase, ASCO, and ESMO conference abstracts were searched. The inclusion criteria were RCT (randomized controlled trials) studies that evaluated the efficacy of anti-EGFR mAbs based on primary tumor location. The outcomes included ORR, ETS, and DpR. ORs for ORR were calculated with 95% confidence intervals by Comprehensive Meta-Analysis, version 2.0.

RESULT

Nine studies including nine RCTs were analyzed. Regardless of left- or right-sided tumors, the ORRs for anti-EGFR mAb (left-sided: 80.2%, 95% CI, 47-95%; I = 76.9%; right-sided: 46.1%, 95% CI, 39.4-53.0%; I = 18.9%) were both higher than the control arm including chemotherapy with or without bevacizumab. The ORs for anti-EGFR mAbs have a significant benefit compared with chemotherapy with or without bevacizumab in left-sided tumors (OR = 2.19, 95% CI, 1.41-3.38; P < 0.001). For right-sided tumors, anti-EGFR mAbs still significantly improved the ORR compared with chemotherapy alone (OR = 1.75, 95% CI, 1.05-2.90; P = 0.03), and the OR numerically favored the anti-EGFR mAbs compared with bevacizumab (OR = 1.281, 95% CI, 0.77-2.12; P = 0.335). The data of ETS and DpR from three RCTs also favored the EGFR antibody irrespective of tumor location. Resection data on differentiating tumor locations is inconclusive. For right-sided tumors, it should be noted that median PFS and OS were comparable for patients who achieved ETS in both treatment arms.

CONCLUSIONS

Anti-EGFR mAbs have advantages in the tumor shrinkage regardless of left- or right-sided tumors, which is important for conversion therapy. For right-sided tumors, anti-EGFR mAbs should remain the first choice for potentially curative resection in RAS wild-type mCRC patients. ETS may represent a subgroup of patients with right-sided tumors who might benefit from the anti-EGFR mAb.

摘要

背景

先前的研究表明，在 RAS 野生型 mCRC（转移性结直肠癌）患者中，左侧肿瘤的预后优于右侧肿瘤，而抗 EGFR mAb 似乎与贝伐珠单抗相比，对右侧肿瘤没有优势。然而，目前尚不清楚原发肿瘤位置是否会影响患者接受潜在治愈性切除的选择。

方法

检索了 PubMed、Cochrane 图书馆、Embase、ASCO 和 ESMO 会议摘要。纳入标准为评估基于原发肿瘤位置的抗 EGFR mAb 疗效的 RCT 研究。结局包括 ORR、ETS 和 DpR。采用 Comprehensive Meta-Analysis，version 2.0 计算 ORR 的 OR，置信区间为 95%。

结果

分析了 9 项研究共 9 项 RCT。无论左侧还是右侧肿瘤，抗 EGFR mAb（左侧：80.2%，95%CI，47-95%；I=76.9%；右侧：46.1%，95%CI，39.4-53.0%；I=18.9%）的 ORR 均高于包括化疗加或不加贝伐珠单抗的对照组。与化疗加或不加贝伐珠单抗相比，抗 EGFR mAb 对左侧肿瘤有显著获益（OR=2.19，95%CI，1.41-3.38；P<0.001）。对于右侧肿瘤，与单独化疗相比，抗 EGFR mAb 仍显著提高了 ORR（OR=1.75，95%CI，1.05-2.90；P=0.03），且与贝伐珠单抗相比，OR 数值上也倾向于抗 EGFR mAb（OR=1.281，95%CI，0.77-2.12；P=0.335）。来自 3 项 RCT 的 ETS 和 DpR 数据也有利于无论肿瘤位置如何使用 EGFR 抗体。区分肿瘤位置的切除数据尚无定论。对于右侧肿瘤，值得注意的是，在治疗组中达到 ETS 的患者的中位 PFS 和 OS 相当。