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

Samuel Martel, Samuel Martel, Marco Bruzzone, Marcello Ceppi, Christian Maurer, Christian Maurer, Noam Falbel Ponde, Arlindo R. Ferreira, Giulia Viglietti, Lucia Del Mastro, Catherine Prady, Evandro de Azambuja, Matteo Lambertini

Research output: Contribution to journalArticle

Abstract

© 2017 Elsevier Ltd. 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.
Original languageEnglish
JournalCancer Treatment Reviews
DOIs
Publication statusAccepted/In press - Sep 26 2017

Keywords

  • Adverse events
  • Endocrine therapy
  • Hormone-receptor positive
  • Metastatic breast cancer
  • Targeted therapy

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