Chen Datian, Li Li, Zhang Xiang, Gao Guangyi, Shen Lili, Hu Jing, Yang Mi, Liu Baorui, Qian Xiaoping
Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University Department of Oncology, Haimen People's Hospital, Haimen The Comprehensive Cancer Center of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University The Comprehensive Cancer Center, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
Medicine (Baltimore). 2018 Mar;97(10):e0097. doi: 10.1097/MD.0000000000010097.
The efficacy of oxaliplatin-based chemotherapy combined with anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) remains controversial in metastatic colorectal cancer (mCRC). This meta-analysis aims to estimate the effect of adding panitumumab or cetuximab to oxaliplatin-based chemotherapy in RAS wild type mCRC patients for the first-line treatment. The primary tumor location is also considered into this meta-analysis.
RCT studies were identified by a search of MEDLINE, EMBASE, Cochrane library to October 2017, supplemented by manually retrieving ASCO, ESMO conference abstracts. The pooled hazard ratio (HR) for progression-free survival (PFS) and overall survival (OS), and pooled odds ratios (OR) for the overall response rate (ORR) were calculated by Review Manager 5.3.
The results indicated that the addition of anti-EGFR mAbs to FOLFOX regimen in RAS wild-type mCRC patients for the first-line treatment resulted in considerable improvements in PFS (HR = 0.70; 95% confidence interval [CI]: 0.59-0.82; P < .0001), OS (HR = 0.79; 95%CI: 0.67-0.92; P = .003), and ORR (OR = 2.56; 95% CI: 1.77-3.70; P < .00001) compared with chemotherapy alone. However, in RAS/BRAF wild patients, no significant differences were observed when anti-EGFR mAb was added to FLOX or XELOX regimen compared with chemotherapy alone with regard to OS and PFS, whereas FOLFOX+anti-EGFR mAb showed a marked superior OS and PFS (OS, HR = 0.77; 95% CI: 0.61-0.98; P = .03; PFS, HR = 0.68; 95% CI: 0.57-0.82; P < .00001). A meta-analysis including TAILOR and PRIME study suggests that primary tumor location (PTL) predicted a survival benefit when adding the EGFR antibody to FOLFOX regimen in RAS-wild mCRC patients (OS, HR for left-sided: 0.71; 95% CI: 0.59-0.85; P = .0002 and HR for right-sided: 0.90; 95% CI: 0.65-1.25; P = .53). However, the HR for PFS and ORR still suggests a benefit from the addition of anti-EGFR mAb in right-sided mCRC patients.
So these results suggest anti-EGFR mAb and oxaliplatin are good partners in the FOLFOX regimen. The addition of EGFR antibody to FOLFOX markedly improved efficacy in RAS-wild patients with left-sided mCRC. In RAS/BRAF-wild patients, the efficacy is similar. For patients with right-sided tumor, a benefit showing a trendency in favor of anti-EGFR mAb can still seen. The molecular characteristics behind the tumor location need to be more explored urgently.
在转移性结直肠癌（mCRC）中，基于奥沙利铂的化疗联合抗表皮生长因子受体（EGFR）单克隆抗体（mAb）的疗效仍存在争议。本荟萃分析旨在评估在RAS野生型mCRC患者一线治疗中，在基于奥沙利铂的化疗基础上加用帕尼单抗或西妥昔单抗的效果。本荟萃分析还考虑了原发肿瘤部位。
通过检索MEDLINE、EMBASE、Cochrane图书馆至2017年10月来确定随机对照试验（RCT）研究，并通过手动检索美国临床肿瘤学会（ASCO）、欧洲肿瘤内科学会（ESMO）会议摘要进行补充。采用Review Manager 5.3计算无进展生存期（PFS）和总生存期（OS）的合并风险比（HR），以及总缓解率（ORR）的合并比值比（OR）。
结果表明，在RAS野生型mCRC患者一线治疗中，在FOLFOX方案基础上加用抗EGFR mAb可使PFS（HR = 0.70；95%置信区间[CI]：0.59 - 0.82；P <.0001）、OS（HR = 0.79；95%CI：0.67 - 0.92；P =.003）和ORR（OR = 2.56；95%CI：1.77 - 3.70；P <.00001）相比单纯化疗有显著改善。然而，在RAS/BRAF野生型患者中，与单纯化疗相比，在FLOX或XELOX方案中加用抗EGFR mAb时，在OS和PFS方面未观察到显著差异，而FOLFOX + 抗EGFR mAb显示出显著优越的OS和PFS（OS，HR = 0.77；95%CI：0.61 - 0.98；P =.03；PFS，HR = 0.68；95%CI：0.57 - 0.82；P <.00001）。一项纳入TAILOR和PRIME研究的荟萃分析表明，在RAS野生型mCRC患者中，当在FOLFOX方案中加用EGFR抗体时，原发肿瘤部位（PTL）可预测生存获益（OS，左侧HR：0.71；95%CI：0.59 - 0.85；P =.0002，右侧HR：0.90；95%CI：0.65 - 1.25；P =.53）。然而，PFS和ORR的HR仍表明在右侧mCRC患者中加用抗EGFR mAb有获益。
因此，这些结果表明抗EGFR mAb和奥沙利铂在FOLFOX方案中是良好的搭档。在FOLFOX方案中加用EGFR抗体可显著提高左侧RAS野生型mCRC患者的疗效。在RAS/BRAF野生型患者中，疗效相似。对于右侧肿瘤患者，仍可看到有利于抗EGFR mAb的获益趋势。肿瘤部位背后的分子特征亟待进一步探索。
