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Heinemann, Volker; Rivera, Fernando; O'Neil, Bert H.; Stintzing, Sebastian; Koukakis, Reija; Terwey, Jan-Henrik; Douillard, Jean-Yves (2016): 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. In: European Journal of Cancer, Vol. 67: pp. 11-20
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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. (C) 2016 The Authors. Published by Elsevier Ltd.