Infectious complications of cyclin-dependent kinases 4 and 6 inhibitors in patients with hormone-receptor-positive metastatic breast cancer: a systematic review and meta-analysis

Aim The combination of cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitors plus endocrine therapy (ET) improved the survival outcomes and became the standard of care in the treatment of metastatic hormone-positive breast cancer. However, these combinations increased the risk of neutropenia compared...

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Bibliographic Details
Published in:Supportive care in cancer 2022-11, Vol.30 (11), p.9071-9078
Main Authors: Bas, Onur, Erul, Enes, Guven, Deniz Can, Aksoy, Sercan
Format: Article
Language:English
Subjects:
Breast cancer
Clinical trials
Comparative analysis
Complications and side effects
Cyclin-dependent kinases
Drug therapy
Hormones
Medical research
Medicine
Medicine & Public Health
Medicine, Experimental
Meta-analysis
Metastasis
Mortality
Neutropenia
Nursing
Nursing Research
Oncology
Original Article
Pain Medicine
Rehabilitation Medicine
Respiratory tract diseases
Targeted cancer therapy
Urinary tract diseases
Urinary tract infections
Urogenital system
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Summary:Aim The combination of cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitors plus endocrine therapy (ET) improved the survival outcomes and became the standard of care in the treatment of metastatic hormone-positive breast cancer. However, these combinations increased the risk of neutropenia compared with ET alone. While the infection-related mortalities did not seem to be increased, the exact risk of infections with CDK 4/6 inhibitor and ET combinations is relatively understudied. Therefore, we performed a meta-analysis of CDK 4/6 inhibitor clinical trials to assess the infection risk of adding CDK4/6 inhibitors to ET. Material and method We systemically searched the PubMed database for relevant clinical trials. For each study, all grade and grade 3 or higher infections, upper respiratory tract infections (URTI), urinary tract infections (UTI), pneumonia, and febrile neutropenia rates were recorded whenever available. The hazard ratios (HR) with a 95% confidence interval (CI) of infection risk were calculated via the generic inverse-variance method with a random-effects model. Results Nine eligible studies were included in the analyses (MONALEESA-2,3,7, MONARCH-2,3, MONARCH plus, PALOMA-1,2,3). In the meta-analysis of these studies, CDK 4/6 inhibitors plus ET arms were associated with increased all grade infections (HR 1.77, 95% CI 1.56–2.01, p  
ISSN:0941-4355
1433-7339
DOI:10.1007/s00520-022-07320-y