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Front. Pharmacol. | doi: 10.3389/fphar.2018.00441

First biologic drug in the treatment of RAS wild-type metastatic colorectal cancer: anti-EGFR or bevacizumab? Results from a meta-analysis.

 Alessandro Ottaiano1, Alfonso De Stefano1, Anna Nappi1,  Monica Capozzi1, Chiara De Divitiis1, Carmela Romano1, Lucrezia Silvestro1, Antonino Cassata1, Rossana Casaretti1,  Salvatore Tafuto1, Michele Caraglia2,  Massimiliano Berretta3, Guglielmo Nasti1 and Antonio Avallone1*
  • 1Abdominal Oncology, Istituto Nazionale Tumori Fondazione G. Pascale (IRCCS), Italy
  • 2Università degli Studi della Campania "Luigi Vanvitelli" Naples, Italy
  • 3Centro di Riferimento Oncologico di Aviano (IRCCS), Italy

Introduction. We performed a meta-analysis in order to analyze and quantify the effect on survival of starting therapy in RAS wild-type (wt) metastatic colorectal cancer (mCRC) patients with anti-EGFR agents or bevacizumab. Patients and Methods. Randomized, phase II or III, clinical trials reporting overall survival (OS) in RAS wt mCRC patients treated with first-line chemotherapy (CT) associated with bevacizumab or anti-EGFR agents were selected. The primary end-point of this meta-analysis was OS; findings were depicted in classical Forest plots. Results. Seven studies met the criteria for meta-analysis including 3805 patients. The pooled second-line cross-over rate to bevacizumab was 36.6%, to anti-EGFR 33.2%. Only one study was selected reporting comparison between CT vs CT plus bevacizumab in RAS wt patients with a HR of 1.13 in favor of CT (CI: 0.89-1.43, p=0.317). The pooled HRs were 0.89 (95% CI: 0.79-1.00) for CT plus anti-EGFR vs CT and 0.81 (95% CI: 0.71-0.92) in favor of CT plus anti-EGFR vs CT plus bevacizumab. Subgroup analysis showed a positive prognostic impact of starting CT plus anti-EGFR in left colon cancer (pooled HR: 0.70; CI: 0.54-0.85) while a positive trend of starting CT plus bevacizumab was observed in right colon cancer (pooled HR: 1.29; CI: 0.81-1.77). Conclusions. This meta-analysis shows that starting therapy in RAS wt mCRC patients with an anti-EGFR agent improves OS when the primary tumor location is in the left colon but a strong limitation of previous studies is the very low rate of biologic drug therapy cross-over.

Keywords: colorectal carcinoma, chemotherapy, cetuximab, Panitumumab, bevacizumab.

Received: 19 Jan 2018; Accepted: 16 Apr 2018.

Edited by:

Salvatore Salomone, Università degli Studi di Catania, Italy

Reviewed by:

Giuseppe Curigliano, Istituto Europeo di Oncologia s.r.l., Italy
Ulf Gunnarsson, Umeå University, Sweden
Hao Liu, Nanfang Hospital, Southern Medical University, China  

Copyright: © 2018 Ottaiano, De Stefano, Nappi, Capozzi, De Divitiis, Romano, Silvestro, Cassata, Casaretti, Tafuto, Caraglia, Berretta, Nasti and Avallone. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Antonio Avallone, Istituto Nazionale Tumori Fondazione G. Pascale (IRCCS), Abdominal Oncology, Napoli, Italy,