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Meta-Analysis
. 2016 Nov:67:11-20.
doi: 10.1016/j.ejca.2016.07.019. Epub 2016 Sep 1.

A study-level meta-analysis of efficacy data from head-to-head first-line trials of epidermal growth factor receptor inhibitors versus bevacizumab in patients with RAS wild-type metastatic colorectal cancer

Volker Heinemann  1 , Fernando Rivera  2 , Bert H O'Neil  3 , Sebastian Stintzing  4 , Reija Koukakis  5 , Jan-Henrik Terwey  6 , Jean-Yves Douillard  7
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Free article
Meta-Analysis

A study-level meta-analysis of efficacy data from head-to-head first-line trials of epidermal growth factor receptor inhibitors versus bevacizumab in patients with RAS wild-type metastatic colorectal cancer

Volker Heinemann et al. Eur J Cancer. 2016 Nov.
Free article

Abstract

Background: Head-to-head trials comparing first-line epidermal growth factor receptor inhibitor (EGFRI) versus vascular endothelial growth factor inhibitor (bevacizumab) therapy yielded differing results, and debate remains over optimal first-line therapy for patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC).

Methods: A PubMed search identified first-line mCRC trials comparing EGFRI plus chemotherapy versus bevacizumab plus chemotherapy; data were subsequently updated using recent congress presentations. This study-level meta-analysis estimated the overall survival (OS) treatment effect of first-line chemotherapy plus EGFRIs or bevacizumab in patients with RAS WT mCRC. Secondary end-points were progression-free survival (PFS), objective response rate (ORR), resection rate and safety. Early tumour shrinkage (ETS) of ≥20% at week 8 was an exploratory end-point.

Results: Three trials comprising data from 1096 patients with RAS WT mCRC were included. OS (hazard ratio [HR]: 0.80 [95% confidence interval: 0.68-0.93]), ORR (odds ratio [OR]: 0.57) and ETS (OR: 0.48) favoured EGFRIs plus chemotherapy versus bevacizumab plus chemotherapy. PFS (HR: 0.98) and resections (OR: 0.93) were similar between treatments. For patients with KRAS exon 2 WT/'other' RAS mutant mCRC the OS HR was 0.70. A safety meta-analysis was not possible due to a lack of data; in the individual studies, skin toxicities and hypomagnesaemia were more common with EGFRIs, nausea and hypertension were more common with bevacizumab.

Conclusions: This meta-analysis supports a potential benefit for first-line EGFRI plus chemotherapy versus bevacizumab plus chemotherapy with respect to OS, ORR and ETS in patients with RAS WT mCRC. A patient-level meta-analysis is awaited.

Keywords: Bevacizumab; Cetuximab; Meta-analysis; Panitumumab; Progression-free survival; Survival.

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