How to Deal with Second Line Dilemma in Metastatic Colorectal Cancer? A Systematic Review and Meta-Analysis

Nadia Barraco, Antonio Russo, Giuseppe Badalamenti, Lorena Incorvaia, Aurelia Ada Guarini, Viviana Bazan, Antonio Galvano, Valentina Calo', Giuseppe Curro', Nicola Silvestris, Giordano Domenico Beretta, Luisa Castellana, Sergio Rizzo, Sofia Cutaia, Stefania Cusenza

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Monoclonal antibodies targeting epidermal growth factor receptor (EGFR) or vascular endothelial growth factor (VEGF) have demonstrated efficacy with chemotherapy (CT) as second line treatment for metastatic colorectal cancer (mCRC). The right sequence of the treatments in all RAS (KRAS/NRAS) wild type (wt) patients has not precisely defined. We evaluated the impact of aforementioned targeted therapies in second line setting, analyzing efficacy and safety data from phase III clinical trials. We performed both direct and indirect comparisons between anti-EGFR and anti-VEGF. Outcomes included disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and G3-G5 toxicities. Our results showed significantly improved OS (HR 0.83, 95% CI 0.72-0.94) and DCR (HR 1.27, 95% CI 1.04-1.54) favouring anti-VEGF combinations in overall population; no statistically significant differences in all RAS wt patients was observed (HR 0.87, 95% CI 0.70-1.09). Anti-EGFR combinations significantly increased ORR in all patients (RR 0.54, 95% CI 0.31-0.96), showing a trend also in all RAS wt patients (RR 0.63, 95% CI 0.48-0.83). No significant difference in PFS and DCR all RAS was registered. Our results provided for the first time a strong rationale to manage both targeted agents in second line setting.
Original languageEnglish
Number of pages11
JournalCancers
Volume11
Publication statusPublished - 2019

Fingerprint

Meta-Analysis
Colorectal Neoplasms
Epidermal Growth Factor Receptor
Vascular Endothelial Growth Factor A
Disease-Free Survival
Phase III Clinical Trials
Survival
Therapeutics
Monoclonal Antibodies
Safety
Drug Therapy
Population

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

How to Deal with Second Line Dilemma in Metastatic Colorectal Cancer? A Systematic Review and Meta-Analysis. / Barraco, Nadia; Russo, Antonio; Badalamenti, Giuseppe; Incorvaia, Lorena; Guarini, Aurelia Ada; Bazan, Viviana; Galvano, Antonio; Calo', Valentina; Curro', Giuseppe; Silvestris, Nicola; Beretta, Giordano Domenico; Castellana, Luisa; Rizzo, Sergio; Cutaia, Sofia; Cusenza, Stefania.

In: Cancers, Vol. 11, 2019.

Research output: Contribution to journalArticle

@article{7ac96713a6964eaa9b0032f3bf2cefc7,
title = "How to Deal with Second Line Dilemma in Metastatic Colorectal Cancer? A Systematic Review and Meta-Analysis",
abstract = "Monoclonal antibodies targeting epidermal growth factor receptor (EGFR) or vascular endothelial growth factor (VEGF) have demonstrated efficacy with chemotherapy (CT) as second line treatment for metastatic colorectal cancer (mCRC). The right sequence of the treatments in all RAS (KRAS/NRAS) wild type (wt) patients has not precisely defined. We evaluated the impact of aforementioned targeted therapies in second line setting, analyzing efficacy and safety data from phase III clinical trials. We performed both direct and indirect comparisons between anti-EGFR and anti-VEGF. Outcomes included disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and G3-G5 toxicities. Our results showed significantly improved OS (HR 0.83, 95{\%} CI 0.72-0.94) and DCR (HR 1.27, 95{\%} CI 1.04-1.54) favouring anti-VEGF combinations in overall population; no statistically significant differences in all RAS wt patients was observed (HR 0.87, 95{\%} CI 0.70-1.09). Anti-EGFR combinations significantly increased ORR in all patients (RR 0.54, 95{\%} CI 0.31-0.96), showing a trend also in all RAS wt patients (RR 0.63, 95{\%} CI 0.48-0.83). No significant difference in PFS and DCR all RAS was registered. Our results provided for the first time a strong rationale to manage both targeted agents in second line setting.",
author = "Nadia Barraco and Antonio Russo and Giuseppe Badalamenti and Lorena Incorvaia and Guarini, {Aurelia Ada} and Viviana Bazan and Antonio Galvano and Valentina Calo' and Giuseppe Curro' and Nicola Silvestris and Beretta, {Giordano Domenico} and Luisa Castellana and Sergio Rizzo and Sofia Cutaia and Stefania Cusenza",
year = "2019",
language = "English",
volume = "11",
journal = "Cancers",
issn = "2072-6694",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

}

TY - JOUR

T1 - How to Deal with Second Line Dilemma in Metastatic Colorectal Cancer? A Systematic Review and Meta-Analysis

AU - Barraco, Nadia

AU - Russo, Antonio

AU - Badalamenti, Giuseppe

AU - Incorvaia, Lorena

AU - Guarini, Aurelia Ada

AU - Bazan, Viviana

AU - Galvano, Antonio

AU - Calo', Valentina

AU - Curro', Giuseppe

AU - Silvestris, Nicola

AU - Beretta, Giordano Domenico

AU - Castellana, Luisa

AU - Rizzo, Sergio

AU - Cutaia, Sofia

AU - Cusenza, Stefania

PY - 2019

Y1 - 2019

N2 - Monoclonal antibodies targeting epidermal growth factor receptor (EGFR) or vascular endothelial growth factor (VEGF) have demonstrated efficacy with chemotherapy (CT) as second line treatment for metastatic colorectal cancer (mCRC). The right sequence of the treatments in all RAS (KRAS/NRAS) wild type (wt) patients has not precisely defined. We evaluated the impact of aforementioned targeted therapies in second line setting, analyzing efficacy and safety data from phase III clinical trials. We performed both direct and indirect comparisons between anti-EGFR and anti-VEGF. Outcomes included disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and G3-G5 toxicities. Our results showed significantly improved OS (HR 0.83, 95% CI 0.72-0.94) and DCR (HR 1.27, 95% CI 1.04-1.54) favouring anti-VEGF combinations in overall population; no statistically significant differences in all RAS wt patients was observed (HR 0.87, 95% CI 0.70-1.09). Anti-EGFR combinations significantly increased ORR in all patients (RR 0.54, 95% CI 0.31-0.96), showing a trend also in all RAS wt patients (RR 0.63, 95% CI 0.48-0.83). No significant difference in PFS and DCR all RAS was registered. Our results provided for the first time a strong rationale to manage both targeted agents in second line setting.

AB - Monoclonal antibodies targeting epidermal growth factor receptor (EGFR) or vascular endothelial growth factor (VEGF) have demonstrated efficacy with chemotherapy (CT) as second line treatment for metastatic colorectal cancer (mCRC). The right sequence of the treatments in all RAS (KRAS/NRAS) wild type (wt) patients has not precisely defined. We evaluated the impact of aforementioned targeted therapies in second line setting, analyzing efficacy and safety data from phase III clinical trials. We performed both direct and indirect comparisons between anti-EGFR and anti-VEGF. Outcomes included disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and G3-G5 toxicities. Our results showed significantly improved OS (HR 0.83, 95% CI 0.72-0.94) and DCR (HR 1.27, 95% CI 1.04-1.54) favouring anti-VEGF combinations in overall population; no statistically significant differences in all RAS wt patients was observed (HR 0.87, 95% CI 0.70-1.09). Anti-EGFR combinations significantly increased ORR in all patients (RR 0.54, 95% CI 0.31-0.96), showing a trend also in all RAS wt patients (RR 0.63, 95% CI 0.48-0.83). No significant difference in PFS and DCR all RAS was registered. Our results provided for the first time a strong rationale to manage both targeted agents in second line setting.

UR - http://hdl.handle.net/10447/367369

M3 - Article

VL - 11

JO - Cancers

JF - Cancers

SN - 2072-6694

ER -