Efficacy and safety of regorafenib in the treatment of metastatic colorectal cancer: A systematic review

Maria Røed Skårderud; Anne Polk; Kirsten Kjeldgaard Vistisen; Finn Ole Larsen; Dorte Lisbet Nielsen

doi:10.1016/j.ctrv.2017.10.011

Efficacy and safety of regorafenib in the treatment of metastatic colorectal cancer: A systematic review

Maria Røed Skårderud, Anne Polk, Kirsten Kjeldgaard Vistisen, Finn Ole Larsen, Dorte Lisbet Nielsen

Department of Clinical Medicine

30 Citations (Scopus)

Abstract

PURPOSE: Despite advances in the treatment of colorectal cancer, third-line treatment options are still limited. Regorafenib was approved in 2012 for the treatment of patients with metastatic colorectal cancer previously treated with approved standard therapy. The purpose of this review is to present existing clinical data on regorafenib.

METHOD: We systematically searched the PubMed and Embase databases, as well as ASCO and ESMO conference abstracts, for studies in English including ≥30 patients, evaluating the efficacy and safety of regorafenib in patients with metastatic colorectal cancer. A meta-analysis was conducted on the published, randomized phase III trials.

RESULTS: 24 eligible studies were included. In two phase III trials, regorafenib significantly increased overall survival (OS), progression free survival (PFS), and disease control rate when compared to placebo. Survival benefits of 1.4 and 2.5 months were presented. The meta-analysis indicated a significant greater treatment effect on OS (hazard ratio 0.67) and PFS (hazard ratio 0.40), compared to placebo. The non-randomized studies mostly supported these results. The most frequently reported adverse events were hand-foot-skin reaction (25%-86%), hypertension (11%-47%) and fatigue (2%-73%).

CONCLUSION: Large phase III randomized trials indicate that regorafenib provides a benefit in OS and PFS when compared to placebo. Adverse events were common, but manageable and typical of multi-target tyrosine kinase inhibitors. Further research is needed to investigate alternative approaches to the dosing of regorafenib and to explore clinical and molecular biomarkers that can guide patient selection.

Original language	English
Journal	Cancer Treatment Reviews
Volume	62
Pages (from-to)	61-73
Number of pages	13
ISSN	0305-7372
DOIs	https://doi.org/10.1016/j.ctrv.2017.10.011
Publication status	Published - Jan 2018

Keywords

Antineoplastic Agents/therapeutic use
Clinical Trials, Phase III as Topic
Colorectal Neoplasms/drug therapy
Disease-Free Survival
Fatigue/chemically induced
Hand-Foot Syndrome/etiology
Humans
Hypertension/chemically induced
Neoplasm Metastasis
Phenylurea Compounds/therapeutic use
Proportional Hazards Models
Pyridines/therapeutic use
Survival Rate

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ctrv.2017.10.011

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title = "Efficacy and safety of regorafenib in the treatment of metastatic colorectal cancer: A systematic review",

abstract = "PURPOSE: Despite advances in the treatment of colorectal cancer, third-line treatment options are still limited. Regorafenib was approved in 2012 for the treatment of patients with metastatic colorectal cancer previously treated with approved standard therapy. The purpose of this review is to present existing clinical data on regorafenib.METHOD: We systematically searched the PubMed and Embase databases, as well as ASCO and ESMO conference abstracts, for studies in English including ≥30 patients, evaluating the efficacy and safety of regorafenib in patients with metastatic colorectal cancer. A meta-analysis was conducted on the published, randomized phase III trials.RESULTS: 24 eligible studies were included. In two phase III trials, regorafenib significantly increased overall survival (OS), progression free survival (PFS), and disease control rate when compared to placebo. Survival benefits of 1.4 and 2.5 months were presented. The meta-analysis indicated a significant greater treatment effect on OS (hazard ratio 0.67) and PFS (hazard ratio 0.40), compared to placebo. The non-randomized studies mostly supported these results. The most frequently reported adverse events were hand-foot-skin reaction (25%-86%), hypertension (11%-47%) and fatigue (2%-73%).CONCLUSION: Large phase III randomized trials indicate that regorafenib provides a benefit in OS and PFS when compared to placebo. Adverse events were common, but manageable and typical of multi-target tyrosine kinase inhibitors. Further research is needed to investigate alternative approaches to the dosing of regorafenib and to explore clinical and molecular biomarkers that can guide patient selection.",

keywords = "Antineoplastic Agents/therapeutic use, Clinical Trials, Phase III as Topic, Colorectal Neoplasms/drug therapy, Disease-Free Survival, Fatigue/chemically induced, Hand-Foot Syndrome/etiology, Humans, Hypertension/chemically induced, Neoplasm Metastasis, Phenylurea Compounds/therapeutic use, Proportional Hazards Models, Pyridines/therapeutic use, Survival Rate",

author = "{R{\o}ed Sk{\aa}rderud}, Maria and Anne Polk and {Kjeldgaard Vistisen}, Kirsten and Larsen, {Finn Ole} and Nielsen, {Dorte Lisbet}",

year = "2018",

month = jan,

doi = "10.1016/j.ctrv.2017.10.011",

language = "English",

volume = "62",

pages = "61--73",

journal = "Cancer Treatment Reviews",

issn = "0305-7372",

publisher = "W.B.Saunders Co. Ltd.",

}

TY - JOUR

T1 - Efficacy and safety of regorafenib in the treatment of metastatic colorectal cancer

T2 - A systematic review

AU - Røed Skårderud, Maria

AU - Polk, Anne

AU - Kjeldgaard Vistisen, Kirsten

AU - Larsen, Finn Ole

AU - Nielsen, Dorte Lisbet

PY - 2018/1

Y1 - 2018/1

N2 - PURPOSE: Despite advances in the treatment of colorectal cancer, third-line treatment options are still limited. Regorafenib was approved in 2012 for the treatment of patients with metastatic colorectal cancer previously treated with approved standard therapy. The purpose of this review is to present existing clinical data on regorafenib.METHOD: We systematically searched the PubMed and Embase databases, as well as ASCO and ESMO conference abstracts, for studies in English including ≥30 patients, evaluating the efficacy and safety of regorafenib in patients with metastatic colorectal cancer. A meta-analysis was conducted on the published, randomized phase III trials.RESULTS: 24 eligible studies were included. In two phase III trials, regorafenib significantly increased overall survival (OS), progression free survival (PFS), and disease control rate when compared to placebo. Survival benefits of 1.4 and 2.5 months were presented. The meta-analysis indicated a significant greater treatment effect on OS (hazard ratio 0.67) and PFS (hazard ratio 0.40), compared to placebo. The non-randomized studies mostly supported these results. The most frequently reported adverse events were hand-foot-skin reaction (25%-86%), hypertension (11%-47%) and fatigue (2%-73%).CONCLUSION: Large phase III randomized trials indicate that regorafenib provides a benefit in OS and PFS when compared to placebo. Adverse events were common, but manageable and typical of multi-target tyrosine kinase inhibitors. Further research is needed to investigate alternative approaches to the dosing of regorafenib and to explore clinical and molecular biomarkers that can guide patient selection.

AB - PURPOSE: Despite advances in the treatment of colorectal cancer, third-line treatment options are still limited. Regorafenib was approved in 2012 for the treatment of patients with metastatic colorectal cancer previously treated with approved standard therapy. The purpose of this review is to present existing clinical data on regorafenib.METHOD: We systematically searched the PubMed and Embase databases, as well as ASCO and ESMO conference abstracts, for studies in English including ≥30 patients, evaluating the efficacy and safety of regorafenib in patients with metastatic colorectal cancer. A meta-analysis was conducted on the published, randomized phase III trials.RESULTS: 24 eligible studies were included. In two phase III trials, regorafenib significantly increased overall survival (OS), progression free survival (PFS), and disease control rate when compared to placebo. Survival benefits of 1.4 and 2.5 months were presented. The meta-analysis indicated a significant greater treatment effect on OS (hazard ratio 0.67) and PFS (hazard ratio 0.40), compared to placebo. The non-randomized studies mostly supported these results. The most frequently reported adverse events were hand-foot-skin reaction (25%-86%), hypertension (11%-47%) and fatigue (2%-73%).CONCLUSION: Large phase III randomized trials indicate that regorafenib provides a benefit in OS and PFS when compared to placebo. Adverse events were common, but manageable and typical of multi-target tyrosine kinase inhibitors. Further research is needed to investigate alternative approaches to the dosing of regorafenib and to explore clinical and molecular biomarkers that can guide patient selection.

KW - Antineoplastic Agents/therapeutic use

KW - Clinical Trials, Phase III as Topic

KW - Colorectal Neoplasms/drug therapy

KW - Disease-Free Survival

KW - Fatigue/chemically induced

KW - Hand-Foot Syndrome/etiology

KW - Humans

KW - Hypertension/chemically induced

KW - Neoplasm Metastasis

KW - Phenylurea Compounds/therapeutic use

KW - Proportional Hazards Models

KW - Pyridines/therapeutic use

KW - Survival Rate

U2 - 10.1016/j.ctrv.2017.10.011

DO - 10.1016/j.ctrv.2017.10.011

M3 - Review

C2 - 29175677

SN - 0305-7372

VL - 62

SP - 61

EP - 73

JO - Cancer Treatment Reviews

JF - Cancer Treatment Reviews

ER -

Efficacy and safety of regorafenib in the treatment of metastatic colorectal cancer: A systematic review

Abstract

Keywords

UN SDGs

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