Volker Heinemann1, Fernando Rivera2, Bert H O'Neil3, Sebastian Stintzing4, Reija Koukakis5, Jan-Henrik Terwey6, Jean-Yves Douillard7. 1. Department of Medical Oncology and Comprehensive Cancer Center, University Hospital Grosshadern, Marchioninistr. 15, D-81377, Munich, Germany. Electronic address: Volker.Heinemann@med.uni-muenchen.de. 2. Department of Medical Oncology, Hospital Universitario Marqués de Valdecilla, Av. de Valdecilla, 39008, Santander, Spain. Electronic address: oncrhf@humv.es. 3. Department of Oncology, Indiana University Simon Cancer Center, 535 Barnhill Drive, Indianapolis, IN, 46202, USA. Electronic address: bhoneil@iu.edu. 4. Department of Medical Oncology and Comprehensive Cancer Center, University Hospital Grosshadern, Marchioninistr. 15, D-81377, Munich, Germany. Electronic address: Sebastian.Stintzing@med.uni-muenchen.de. 5. Biostatistics, Amgen Ltd, 1 Uxbridge Business Park, Sanderson Road, Uxbridge, Middlesex, UB8 1DH, UK. Electronic address: reijak@amgen.com. 6. Medical Development, Amgen Switzerland AG, Dammstrasse 23, 6301, Zug, Switzerland. Electronic address: jan-henrik.terwey@amgen.com. 7. Department of Medical Oncology, Institut de Cancérologie de l'Ouest (ICO) René Gauducheau, 44805, St Herblain, France. Electronic address: jean-yves.douillard@esmo.org.
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.
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.
Authors: B González Astorga; F Salvà Ballabrera; E Aranda Aguilar; E Élez Fernández; P García-Alfonso; E González Flores; R Vera García; A Fernández Montes; A M López Muñoz; A Salud Salvia Journal: Clin Transl Oncol Date: 2021-02-25 Impact factor: 3.405
Authors: Julien Taieb; Fernando Rivera; Salvatore Siena; Meinolf Karthaus; Manuel Valladares-Ayerbes; Javier Gallego; Michael Geissler; Reija Koukakis; Gaston Demonty; Marc Peeters Journal: J Cancer Res Clin Oncol Date: 2017-10-28 Impact factor: 4.553
Authors: Marc Peeters; Frédéric Forget; Meinolf Karthaus; Manuel Valladares-Ayerbes; Alberto Zaniboni; Gaston Demonty; Xuesong Guan; Fernando Rivera Journal: ESMO Open Date: 2018-02-24