Carlo Messina1,2, Carlo Cattrini3,4, Giulia Buzzatti3,4, Luigi Cerbone3,4, Elisa Zanardi3,4, Marco Messina5, Francesco Boccardo3,4. 1. Academic Unit of Medical Oncology, Policlinico Hospital San Martino-IST, Largo R. Benzi 10, 16132, Genoa, Italy. carlo.messi@hotmail.it. 2. Department of Internal Medicine, School of Medicine, University of Genoa, Genoa, Italy. carlo.messi@hotmail.it. 3. Academic Unit of Medical Oncology, Policlinico Hospital San Martino-IST, Largo R. Benzi 10, 16132, Genoa, Italy. 4. Department of Internal Medicine, School of Medicine, University of Genoa, Genoa, Italy. 5. Oncology Unit, Istituto Fondazione G. Giglio, Cefalù, Italy.
Abstract
PURPOSE: Combining CDK4/6 inhibitors and endocrine therapy (ET) improved outcomes for the treatment of metastatic HR+/HER2- breast cancers. Here, we performed a meta-analysis of randomized clinical trials (RCTs) to better define the benefit and the risk of CDK4/6 inhibitors plus ET for endocrine-sensitive or endocrine-resistant population in metastatic HR+/HER2- breast cancer. METHOD: A systematic literature search of Pubmed, Embase, and the Cochrane Library was carried out up to 30 June 2018. Hazard ratios (HRs) and 95% confidence intervals (CIs) for progression-free survival (PFS), as well as odds ratios (ORs) for objective response rates, ≥ G3-G4 adverse events (AEs), and G3-G4 neutropenia were calculated for each trial. A meta-analysis was carried out using the random-effects model. RESULTS: Eight RCTs were eligible including 4578 breast cancer patients. Adding CDK4/6 inhibitors to ET in endocrine-sensitive (HR 0.55, 95% CI 0.50-0.62) or endocrine-resistant setting (HR 0.51, 95% CI 0.43-0.61) significantly improved the PFS of metastatic HR+/HER2- breast cancers regardless of menopausal status and site of metastasis. Moreover, CDK4/6 inhibitors plus ET meaningfully improved objective response rate in endocrine-sensitive (ORs 0.62, 95% CI 0.52-0.73) or endocrine-resistant setting (ORs 0.33, 95% CI 0.24-0.47). The use of these drugs was characterized by a significant increase of G3-G4 AEs (OR 10.88, 95% CI 6.53-18.14). CONCLUSION: Emerging data provide a new standard treatment for advanced HR+/HER2- breast cancer, regardless of menopausal status, prior hormonal/chemotherapy treatments delivered, sites of metastasis. However, benefits should be balanced with longer treatment duration, toxicities, and costs.
PURPOSE: Combining CDK4/6 inhibitors and endocrine therapy (ET) improved outcomes for the treatment of metastatic HR+/HER2- breast cancers. Here, we performed a meta-analysis of randomized clinical trials (RCTs) to better define the benefit and the risk of CDK4/6 inhibitors plus ET for endocrine-sensitive or endocrine-resistant population in metastatic HR+/HER2- breast cancer. METHOD: A systematic literature search of Pubmed, Embase, and the Cochrane Library was carried out up to 30 June 2018. Hazard ratios (HRs) and 95% confidence intervals (CIs) for progression-free survival (PFS), as well as odds ratios (ORs) for objective response rates, ≥ G3-G4 adverse events (AEs), and G3-G4 neutropenia were calculated for each trial. A meta-analysis was carried out using the random-effects model. RESULTS: Eight RCTs were eligible including 4578 breast cancerpatients. Adding CDK4/6 inhibitors to ET in endocrine-sensitive (HR 0.55, 95% CI 0.50-0.62) or endocrine-resistant setting (HR 0.51, 95% CI 0.43-0.61) significantly improved the PFS of metastatic HR+/HER2- breast cancers regardless of menopausal status and site of metastasis. Moreover, CDK4/6 inhibitors plus ET meaningfully improved objective response rate in endocrine-sensitive (ORs 0.62, 95% CI 0.52-0.73) or endocrine-resistant setting (ORs 0.33, 95% CI 0.24-0.47). The use of these drugs was characterized by a significant increase of G3-G4 AEs (OR 10.88, 95% CI 6.53-18.14). CONCLUSION: Emerging data provide a new standard treatment for advanced HR+/HER2- breast cancer, regardless of menopausal status, prior hormonal/chemotherapy treatments delivered, sites of metastasis. However, benefits should be balanced with longer treatment duration, toxicities, and costs.
Entities:
Keywords:
Abemaciclib; Breast cancer; Hormonal therapy; Meta-analysis; Palbociclib; Ribociclib
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