PD-013 - A study level meta-analysis of efficacy data from head-to-head first-line trials of epidermal growth factor receptor inhibitors (EGFRIs) vs bevacizu...

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Anticancer Agents
Colon and Rectal Cancer
Biological Therapy
Presenter V. Heinemann
Citation Annals of Oncology (2015) 26 (suppl_4): 101-107. 10.1093/annonc/mdv234
Authors V. Heinemann1, J. Douillard2, F. Rivera3, B. O'Neill4, R. Koukakis5, J.H. Terwey6
  • 1Medizinische Klinik und Poliklinik III, München/DE
  • 2ICO R. Gauducheau, St Herblain/FR
  • 3Hospital Universitario Marques de Valdecilla, Santander/ES
  • 4Indiana University Simon Cancer Center, Indianapolis/US
  • 5Amgen Ltd, Uxbridge/UK
  • 6Amgen Switzerland AG, Zug/CH



The EGFRIs, panitumumab and cetuximab, and the vascular endothelial growth factor inhibitor, bevacizumab, are all standard first-line treatment options that are used in combination with chemotherapy for patients with mCRC. Data from three head-to-head trials have recently been reported evaluating EGFRIs vs bevacizumab in patients with mCRC. The aim of this study-level meta-analysis was to estimate the relative efficacy of EGFRIs + chemotherapy vs bevacizumab + chemotherapy when administered as first-line treatments for patients with RAS wild-type (WT) mCRC.


This meta-analysis included three pre-defined head-to-head first-line mCRC studies: CALGB 80405 (phase III; bevacizumab or cetuximab + FOLFOX or FOLFIRI), FIRE-3 (phase III; cetuximab + FOLFIRI vs bevacizumab + FOLFIRI) and PEAK (phase II; panitumumab + FOLFOX vs bevacizumab + FOLFOX). No formal hypothesis was tested. The primary objective was to estimate the treatment effect on overall survival (OS) of EGFRIs + chemotherapy vs bevacizumab + chemotherapy; secondary objectives included estimation of the treatment effect on progression-free survival (PFS) and objective response rate (ORR). Meta-analysis techniques, including fixed effects modelling (unconditional maximum likelihood method) and random effects modelling (DerSimonian and Laird modelling methods), were used to pool study-level trial data using the inverse-variance of each study as the weight. Data cut-off for this analysis: December 2014; Data sources: ASCO 2014, ESMO 2014 and JCO 2014;32:2240-7.


These studies included a total of 1038 patients with RAS WT mCRC, which comprised 526, 342 and 170 patients from the CALGB, FIRE-3 and PEAK trials, respectively. Weighted meta-analysis results for OS (hazard ratio [HR]: 0.79 [95% confidence intervals {CI}: 0.67, 0.93) favoured EGFRIs + chemotherapy vs bevacizumab + chemotherapy. In the PFS analysis, the HR (95% CI) for EGFRI + chemotherapy vs bevacizumab + chemotherapy was 0.98 (0.85-1.12). The ORR (rate ratio: 0.81 [95% CI: 0.69, 0.96]) favoured EGFRIs + chemotherapy vs bevacizumab + chemotherapy and the ORR relative difference (95% CI) for bevacizumab + chemotherapy (%) minus EGFRIs + chemotherapy (%) was -12.8 (−18.9, −6.77).


Chemotherapy combined with EGFRIs or bevacizumab are effective first-line treatment options. This meta-analysis suggests that the HR for OS favours EGFRIs over bevacizumab in first-line RAS WT mCRC, although the analysis is limited by differences in study design and the difficulties in assessing the impact of subsequent therapies. The comparative efficacy and safety of the available first-line treatment options need to be carefully considered as part of the overall treatment strategy of patients with RAS WT mCRC. A patient-level meta-analysis to confirm these findings is warranted.