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Open AccessReview

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

1
Medical Oncology, Department of Surgical, Oncological and Stomatological Sciences, University of Palermo, 90127 Palermo, Italy
2
Medical oncology Unit–IRCCS Istituto Tumori “Giovanni Paolo II”, 70124 Bari, Italy
3
Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, 70124 Bari, Italy
4
Medical Oncology Unit Humanitas Gavazzeni, 24125 Bergamo, Italy
5
Department of Biomedicine, Neuroscience and Advanced Diagnostics-BIND, University of Palermo, 90127 Palermo, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Co-last authors.
Cancers 2019, 11(8), 1189; https://doi.org/10.3390/cancers11081189
Received: 12 June 2019 / Revised: 16 July 2019 / Accepted: 16 July 2019 / Published: 15 August 2019
(This article belongs to the Special Issue Colorectal Cancers)
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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. View Full-Text
Keywords: meta-analysis; colorectal cancer; second line; targeted agents; sequence; VEGF; EGFR meta-analysis; colorectal cancer; second line; targeted agents; sequence; VEGF; EGFR
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Galvano, A.; Incorvaia, L.; Badalamenti, G.; Rizzo, S.; Guarini, A.; Cusenza, S.; Castellana, L.; Barraco, N.; Calò, V.; Cutaia, S.; Currò, G.; Silvestris, N.; Beretta, G.D.; Bazan, V.; Russo, A. How to Deal with Second Line Dilemma in Metastatic Colorectal Cancer? A Systematic Review and Meta-Analysis. Cancers 2019, 11, 1189.

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