The efficacy of adding targeted agents to neoadjuvant therapy for locally advanced rectal cancer patients: a meta-analysis

Xi Zhong, Zhonghua Wu, Peng Gao, Jinxin Shi, Jingxu Sun, Zhexu Guo, Zhenning Wang, Yongxi Song, Xi Zhong, Zhonghua Wu, Peng Gao, Jinxin Shi, Jingxu Sun, Zhexu Guo, Zhenning Wang, Yongxi Song

Abstract

Patients with locally advanced rectal cancer (LARC) are at tremendous risk of metastatic diseases. To improve the prognoses of LARC patients, the efficacy of adding targeted agents to neoadjuvant therapy has been investigated by many researchers but remains controversial. A literature search of relevant databases was conducted through December 2016, 804 studies were identified and 32 investigations were ultimately included. A total of 1196 patients from 31 cohorts of 29 studies were eligible for quantitative synthesis in this single-arm setting meta-analysis. As pathologic complete response (pCR) shows promise as a prognosis indicator, we focused on pCR rates to evaluate whether adding targeted agents to neoadjuvant therapies improves the outcome of LARC patients. In our study, we revealed pooled estimates of pCR of 27% (95%CI, 21-34%) and 14% (95%CI, 9-21%) for bevacizumab-relevant cohorts and cetuximab-relevant cohorts, respectively. The safety of adding targeted agents to neoadjuvant therapy was also evaluated by pooling the data of Grade 3/4 toxicity. In conclusion, our study revealed that adding bevacizumab to the neoadjuvant therapy regimens provides appreciable pCR for LARC patients. Meanwhile, the efficacy of cetuximab remains inconclusive, RCTs with larger scale and better study design that stress more on mutational status are needed.

Keywords: Efficacy; neoadjuvant therapy; pathologic complete response; rectal cancer; targeted agents.

© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Selection of studies. Flow diagram showing the selection process for the included studies.
Figure 2
Figure 2
(A) The pooled estimate of pCR for bevacizumab‐relevant cohorts. (B) The results of subgroup analysis of bevacizumab‐relevant cohorts. The pooled estimates of pCR. pCR, pathologic complete response.
Figure 3
Figure 3
(A) The pooled estimate of preoperative Grade 3/4 toxicity for bevacizumab‐relevant cohorts. (B) The results of subgroup analysis of bevacizumab‐relevant cohorts. The pooled estimates of preoperative Grade 3/4 toxicity.
Figure 4
Figure 4
The pooled estimate of pathologic complete response for cetuximab‐relevant cohorts.

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