Universität zu Köln

Martel, Samuel, Bruzzone, Marco ORCID: 0000-0002-8821-4542, Ceppi, Marcello ORCID: 0000-0002-8177-8003, Maurer, Christian, Ponde, Noam Falbel, Ferreira, Arlindo R., Viglietti, Giulia, Del Mastro, Lucia ORCID: 0000-0002-9546-5841, Prady, Catherine, de Azambuja, Evandro ORCID: 0000-0001-9501-4509 and Lambertini, Matteo ORCID: 0000-0003-1797-5296 (2018). Risk of adverse events with the addition of targeted agents to endocrine therapy in patients with hormone receptor-positive metastatic breast cancer: A systematic review and meta-analysis. Cancer Treat. Rev., 62. S. 123 - 133. OXFORD: ELSEVIER SCI LTD. ISSN 1532-1967

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Abstract

Background: Combining targeted agents and endocrine therapy (ET) improves outcomes in hormone receptor-positive metastatic breast cancer patients but increases the risk of Adverse events (AEs). This meta-analysis aims to estimate the comparative risk of AEs with ET in addition to targeted agents in this setting. Methods: A systematic literature search of MEDLINE, EMBASE, Cochrane Library and conference proceedings up to July 17th 2017 was conducted to identify randomized controlled trials investigating ET with or without CDK4/6, mTOR, PI3K inhibitors and anti-HER2 agents. We calculated summary risk estimates (odds ratio, OR) and 95% confidence intervals (CI) for each AE within each class of targeted agents for each trial, and pooled analysis using the random and fixed effect models. Results: Sixteen studies (n = 8529 patients) were included. The addition of targeted agents to ET was associated with a significant higher risk of grade 3-4 AEs: OR 2.86 (95% CI 2.49-3.27) for CDK4/6 inhibitors, 1.88 (95% CI 1.39-2.53) for mTOR inhibitors, 2.05 (95% CI 1.63-2.58) for PI3K inhibitors, and 2.48 (95% CI 1.09-5.66) for anti-HER2 agents. The highest class-specific risks were neutropenia grade 3-4 for CDK4/6 inhibitors (OR 40.77; 95% CI 19.52-85.19), stomatitis grade 3-4 for mTOR inhibitors (OR 11.92; 95% CI 3.68-38.57), hyperglycemia grade 3-4 for PI3K inhibitors (OR 40.93; 95% CI 10.08-166.22) and diarrhea for anti-HER2 agents (OR 9.93; 95% CI 4.71-20.95). Conclusions: Adding targeted agents to ET is associated with a significant increased risk of AEs. The risk of developing different AEs varies largely according to the type of agent used. (C) 2017 Elsevier Ltd. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Martel, Samuel UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruzzone, Marco UNSPECIFIED orcid.org/0000-0002-8821-4542 UNSPECIFIED Ceppi, Marcello UNSPECIFIED orcid.org/0000-0002-8177-8003 UNSPECIFIED Maurer, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Ponde, Noam Falbel UNSPECIFIED UNSPECIFIED UNSPECIFIED Ferreira, Arlindo R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Viglietti, Giulia UNSPECIFIED UNSPECIFIED UNSPECIFIED Del Mastro, Lucia UNSPECIFIED orcid.org/0000-0002-9546-5841 UNSPECIFIED Prady, Catherine UNSPECIFIED UNSPECIFIED UNSPECIFIED de Azambuja, Evandro UNSPECIFIED orcid.org/0000-0001-9501-4509 UNSPECIFIED Lambertini, Matteo UNSPECIFIED orcid.org/0000-0003-1797-5296 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-204181
DOI:	10.1016/j.ctrv.2017.09.009
Journal or Publication Title:	Cancer Treat. Rev.
Volume:	62
Page Range:	S. 123 - 133
Date:	2018
Publisher:	ELSEVIER SCI LTD
Place of Publication:	OXFORD
ISSN:	1532-1967
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GROWTH-FACTOR RECEPTOR; DOUBLE-BLIND; POSTMENOPAUSAL WOMEN; 1ST-LINE TREATMENT; AMERICAN SOCIETY; FULVESTRANT; PLACEBO; EVEROLIMUS; LETROZOLE; PALBOCICLIB Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/20418