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

Publication date: Available online 3 November 2017
Source:Cancer Treatment Reviews
Author(s): Samuel Martel, Marco Bruzzone, Marcello Ceppi, Christian Maurer, Noam Falbel Ponde, Arlindo R. Ferreira, Giulia Viglietti, Lucia Del Mastro, Catherine Prady, Evandro de Azambuja, Matteo Lambertini
BackgroundCombining 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.MethodsA 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.ResultsSixteen 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).ConclusionsAdding 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.



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