First Biologic Drug in the Treatment of RAS Wild-Type Metastatic Colorectal Cancer: Anti-EGFR or Bevacizumab? Results From a Meta-Analysis

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Abstract

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 3,805 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.

Original languageEnglish
Pages (from-to)441
JournalFrontiers in Pharmacology
Volume9
DOIs
Publication statusPublished - 2018

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Meta-Analysis
Colorectal Neoplasms
Drug Therapy
Pharmaceutical Preparations
Therapeutics
Survival
Colonic Neoplasms
Bevacizumab
Biological Therapy
Colon
Clinical Trials

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@article{591e5a1db0e4448db3e2d1179183e82a,
title = "First Biologic Drug in the Treatment of RAS Wild-Type Metastatic Colorectal Cancer: Anti-EGFR or Bevacizumab? Results From a Meta-Analysis",
abstract = "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 3,805 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.",
author = "Alessandro Ottaiano and {De Stefano}, Alfonso and Monica Capozzi and Anna Nappi and {De Divitiis}, Chiara and Carmela Romano and Lucrezia Silvestro and Antonino Cassata and Rossana Casaretti and Salvatore Tafuto and Michele Caraglia and Massimiliano Berretta and Guglielmo Nasti and Antonio Avallone",
year = "2018",
doi = "10.3389/fphar.2018.00441",
language = "English",
volume = "9",
pages = "441",
journal = "Frontiers in Pharmacology",
issn = "1663-9812",
publisher = "Frontiers Media S.A.",

}

TY - JOUR

T1 - First Biologic Drug in the Treatment of RAS Wild-Type Metastatic Colorectal Cancer

T2 - Anti-EGFR or Bevacizumab? Results From a Meta-Analysis

AU - Ottaiano, Alessandro

AU - De Stefano, Alfonso

AU - Capozzi, Monica

AU - Nappi, Anna

AU - De Divitiis, Chiara

AU - Romano, Carmela

AU - Silvestro, Lucrezia

AU - Cassata, Antonino

AU - Casaretti, Rossana

AU - Tafuto, Salvatore

AU - Caraglia, Michele

AU - Berretta, Massimiliano

AU - Nasti, Guglielmo

AU - Avallone, Antonio

PY - 2018

Y1 - 2018

N2 - 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 3,805 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.

AB - 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 3,805 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.

U2 - 10.3389/fphar.2018.00441

DO - 10.3389/fphar.2018.00441

M3 - Review article

VL - 9

SP - 441

JO - Frontiers in Pharmacology

JF - Frontiers in Pharmacology

SN - 1663-9812

ER -