PMID- 29108713 OWN - NLM STAT- MEDLINE DCOM- 20180102 LR - 20211204 IS - 1532-1967 (Electronic) IS - 0305-7372 (Linking) VI - 62 DP - 2018 Jan TI - 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. PG - 123-132 LID - S0305-7372(17)30154-8 [pii] LID - 10.1016/j.ctrv.2017.09.009 [doi] AB - 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. CI - Copyright (c) 2017 Elsevier Ltd. All rights reserved. FAU - Martel, Samuel AU - Martel S AD - Department of Medical Oncology, Institut Jules Bordet, Universite Libre de Bruxelles (U.L.B), Brussels, Belgium; Department of Hemato-Oncology, CISSS Monteregie Centre/Hopital Charles Lemoyne, Universite de Sherbrooke, Greenfield Park, QC, Canada. FAU - Bruzzone, Marco AU - Bruzzone M AD - Unit of Clinical Epidemiology, Ospedale Policlinico San Martino-IST, Genova, Italy. FAU - Ceppi, Marcello AU - Ceppi M AD - Unit of Clinical Epidemiology, Ospedale Policlinico San Martino-IST, Genova, Italy. FAU - Maurer, Christian AU - Maurer C AD - Department of Medical Oncology, Institut Jules Bordet, Universite Libre de Bruxelles (U.L.B), Brussels, Belgium; Department I of Internal Medicine and Center of Integrated Oncology Cologne Bonn, University of Cologne, Cologne, Germany. FAU - Ponde, Noam Falbel AU - Ponde NF AD - Department of Medical Oncology, Institut Jules Bordet, Universite Libre de Bruxelles (U.L.B), Brussels, Belgium. FAU - Ferreira, Arlindo R AU - Ferreira AR AD - Hospital de Santa Maria and Instituto de Medicina Molecular, Faculdade de Leducuba, Universidade de Lisboa, Lisbon, Portugal. FAU - Viglietti, Giulia AU - Viglietti G AD - Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Universite Libre de Bruxelles (U.L.B), Brussels, Belgium. FAU - Del Mastro, Lucia AU - Del Mastro L AD - Department of Medical Oncology, U.O. Sviluppo Terapie Innovative, Ospedale Policlinico San Martino-IST, Genova, Italy. FAU - Prady, Catherine AU - Prady C AD - Department of Hemato-Oncology, CISSS Monteregie Centre/Hopital Charles Lemoyne, Universite de Sherbrooke, Greenfield Park, QC, Canada. FAU - de Azambuja, Evandro AU - de Azambuja E AD - Department of Medical Oncology, Institut Jules Bordet, Universite Libre de Bruxelles (U.L.B), Brussels, Belgium. FAU - Lambertini, Matteo AU - Lambertini M AD - Department of Medical Oncology, Institut Jules Bordet, Universite Libre de Bruxelles (U.L.B), Brussels, Belgium; Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Universite Libre de Bruxelles (U.L.B), Brussels, Belgium. Electronic address: matteo.lambertini@bordet.be. LA - eng PT - Journal Article PT - Meta-Analysis PT - Review PT - Systematic Review DEP - 20171103 PL - Netherlands TA - Cancer Treat Rev JT - Cancer treatment reviews JID - 7502030 RN - 0 (Antineoplastic Agents, Hormonal) RN - 0 (Phosphoinositide-3 Kinase Inhibitors) RN - 0 (Receptors, Estrogen) RN - 0 (Receptors, Progesterone) RN - EC 2.7.10.1 (ERBB2 protein, human) RN - EC 2.7.10.1 (Receptor, ErbB-2) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.11.22 (Cyclin-Dependent Kinase 4) RN - EC 2.7.11.22 (Cyclin-Dependent Kinase 6) SB - IM MH - Antineoplastic Agents, Hormonal/administration & dosage/adverse effects MH - Antineoplastic Combined Chemotherapy Protocols/*adverse effects MH - Breast Neoplasms/*drug therapy/metabolism/pathology MH - Cyclin-Dependent Kinase 4/antagonists & inhibitors MH - Cyclin-Dependent Kinase 6/antagonists & inhibitors MH - Diarrhea/*chemically induced MH - Humans MH - Hyperglycemia/*chemically induced MH - Molecular Targeted Therapy MH - Neutropenia/*chemically induced MH - Odds Ratio MH - Phosphoinositide-3 Kinase Inhibitors MH - Receptor, ErbB-2/antagonists & inhibitors MH - Receptors, Estrogen/metabolism MH - Receptors, Progesterone/metabolism MH - TOR Serine-Threonine Kinases/antagonists & inhibitors OTO - NOTNLM OT - Adverse events OT - Endocrine therapy OT - Hormone-receptor positive OT - Metastatic breast cancer OT - Targeted therapy EDAT- 2017/11/08 06:00 MHDA- 2018/01/03 06:00 CRDT- 2017/11/08 06:00 PHST- 2017/09/26 00:00 [received] PHST- 2017/09/27 00:00 [accepted] PHST- 2017/11/08 06:00 [pubmed] PHST- 2018/01/03 06:00 [medline] PHST- 2017/11/08 06:00 [entrez] AID - S0305-7372(17)30154-8 [pii] AID - 10.1016/j.ctrv.2017.09.009 [doi] PST - ppublish SO - Cancer Treat Rev. 2018 Jan;62:123-132. doi: 10.1016/j.ctrv.2017.09.009. Epub 2017 Nov 3.