Chemotherapy With or Without Anti-EGFR Agents in Left- and Right-Sided Metastatic Colorectal Cancer: An Updated Meta-Analysis

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Abstract

Background: Previous meta-analyses have suggested primary tumor location as a predictive factor for efficacy of anti–epidermal growth factor receptor (EGFR) therapies in patients with metastatic colorectal cancer (mCRC). However, the recent phase III TAILOR trial addressing this issue was not included in those analyses. This meta-analysis incorporated data from the TAILOR trial to evaluate the efficacy of chemotherapy plus anti-EGFR agents (cetuximab [Cet] or panitumumab [Pani]) versus chemotherapy alone for RAS wild-type (wt) right- and left-sided mCRC. Patients and Methods: A PubMed-based literature search was conducted to identify randomized controlled trials (RCTs) studying the additional efficacy of Cet/Pani in combination with chemotherapy versus chemotherapy alone in RAS wt left- and right-sided mCRC. Study-level pooled analyses of hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and odds ratios (ORs) for objective response rate (ORR) were performed. Results: Three first-line RCTs (CRYSTAL, PRIME, and TAILOR) and one second-line RCT (20050181) were included. Significant OS benefits from Cet/Pani were observed in the left-sided (HR, 0.76; 95% CI, 0.66–0.86) but not right-sided subgroups (HR, 0.99; 95% CI, 0.78–1.27). However, the addition of Cet/Pani to chemotherapy significantly improved PFS and ORR in both the left-sided (HR, 0.70; 95% CI, 0.57–0.86, and OR, 3.28; 95% CI, 1.95–5.51, respectively) and right-sided subgroups (HR, 0.76; 95% CI, 0.59–0.99, and OR, 1.78; 95% CI, 1.08–2.93, respectively). Conclusions: The addition of Cet/Pani to chemotherapy significantly benefits PFS and ORR in patients with RAS wt right-sided mCRC, indicating that anti-EGFR therapies may remain an option for selected patients.

Submitted June 25, 2018; accepted for publication January 28, 2019.Author contributions: Study concept and design: Z.X. Wang, Wu, Xu. Literature retrieval: Z.X. Wang, Wu. Data acquisition & risk of bias assessment: Z.X. Wang, Wu, He, Luo, Ding, Xie, Chen, Li, F. Wang, Xu. Data analysis and interpretation: Z.X. Wang, Wu, He, Y.N. Wang, Xu. Manuscript preparation: Z.X. Wang, Wu. Critical revisions: All authors.Disclosures: The authors have disclosed that they have not received any financial considerations from any person or organization to support the preparation, analysis, results, or discussion of this article.Funding: This study was supported by grants from the Natural Science Foundation of Guangdong Province (2014A030312015), Science and Technology Program of Guangdong (2015B020232008), and Science and Technology Program of Guangzhou (15570006, 201508020250, 201604020003).Correspondence: Rui-Hua Xu, MD, PhD, Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dong Feng Road East, Guangzhou 510060, China. Email: xurh@sysucc.org.cn
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