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Poster display session

4526 - The CAN BEAR study: a systematic review and meta-analysis investigating adverse events (AEs) of targeted agents added to endocrine therapy (ET) in patients (pts) with hormone-receptor positive (HR+) metastatic breast cancer (MBC)


11 Sep 2017


Poster display session


Cytotoxic Therapy;  Supportive Care and Symptom Management;  Targeted Therapy;  Breast Cancer


Samuel Martel


Annals of Oncology (2017) 28 (suppl_5): v74-v108. 10.1093/annonc/mdx365


S. Martel1, M. Bruzzone2, M. Ceppi2, C. Maurer1, N. Falbel Ponde1, A.R. Ferreira1, G. Viglietti3, L. Delmastro4, C. Prady5, E. De Azambuja1, M. Lambertini3

Author affiliations

  • 1 Oncologie Médicale, Institut Jules Bordet, 1000 - Bruxelles/BE
  • 2 Clinical Epidemiology, IRCCS AOU San Martino-IST, National Institute for Cancer Research, 16132 - Genova/IT
  • 3 Breast Cancer Translational Research Laboratory, Institute Jules Bordet, 1000 - Brussels/BE
  • 4 Department Of Oncology, IRCCS AOU, 16132 - San Martino-IST/IT
  • 5 Oncologie Médicale, Hôpital Charles-Lemoyne, J4V 2H1 - Greenfield Park/CA


Abstract 4526


Combining targeted agents and ET improves outcomes in pts with HR+ MBC but increases the risk of AEs. However, the specific additional toxicity burden caused by these agents remains unknown. Our meta-analysis aims to better estimate the comparative risk of AEs with the combination of ET and CDK4/6 inhibitors, PI3K inhibitors, mTOR inhibitors and anti-HER2 agents in pts with HR+ MBC.


A systematic literature search of MEDLINE, EMBASE, Cochrane Library and proceedings from major conferences up to March 31st 2017 was conducted to identify randomized controlled trials investigating ET plus CDK4/6, PI3K, mTOR inhibitors and anti-HER2 agents as compared to ET alone in pts with HR+ MBC. For each class of targeted agents, two groups were considered: ET plus targeted agent vs. ET alone. Summary risk estimates (odds ratio, OR) and 95% confidence intervals (CI) were calculated for each side effect within each class of targeted agents for each trial. Pooled analysis was conducted using the random and fixed effects models.


A total of 7865 pts from 15 studies were included in our meta-analysis. Overall, the addition of targeted agents to ET was associated with significant higher risk of grade 3-4 AEs: OR 2.95 (95% CI 2.47-3.53) for CDK4/6 inhibitors, 2.05 (95% CI 1.63-2.58) for PI3K inhibitors, 1.89 (95% CI 1.40-2.56) for mTOR inhibitors, and 2.33 (95% CI 1.17-4.63) for anti-HER2 agents. Anti-HER2 agents, CDK4/6 and PI3K inhibitors significantly increased the risk of grade 3-4 fatigue, but not mTOR inhibitors (OR 1.48; 95% CI 0.64-3.43). Anti-HER2 agents, PI3K and mTOR inhibitors significantly increased the risk of grade 3-4 diarrhea, but not CDK4/6 inhibitors (OR 1.15; 95% CI 0.46-2.87). Other AEs and class specific toxicities will be reported at the conference.


In pts with HR+ MBC, the combination of targeted agents and ET is associated with significant increased risk of AEs. The risk of developing different AEs varies largely according to the type of agent used. Potential specific toxicities should be taken into account and discussed with patients when deciding to opt for combination regimens.

Clinical trial identification

PROSPERO registration number: CRD42017058278

Legal entity responsible for the study

Samuel Martel




E. De Azambuja: Honoraria from Roche and travel grants from Roche and GlaxoSmithKline outside the submitted work. All other authors have declared no conflicts of interest.

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