Summary

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• This summary is based on the review of 15 systematic review(s)/meta-analysis(es). ^[1-15]
• Effectiveness of Cyclin-Dependent Kinase (CDK)4/6 Inhibitors with Endocrine Therapy (ET): Abemaciclib, Dalpiciclib, Palbociclib, and Ribociclib combined with ET demonstrated similar effectiveness in improving objective response rates (ORR) and disease control rates (DCR), all significantly outperforming ET alone. Ribociclib + ET showed superior overall survival (OS) compared to Palbociclib + ET, while Dalpiciclib + ET significantly improved progression-free survival (PFS) compared to the other CDK4/6 inhibitors.
• Impact of Proton Pump Inhibitors (PPIs): Concomitant use of PPIs with Palbociclib was associated with significantly increased risks of all-cause mortality and disease progression, a relationship not observed with Ribociclib.
• Quality of Life (health-related quality of life (HR-QoL)) Outcomes: Adding CDK4/6 inhibitors to ET did not worsen HR-QoL and even showed trends toward pain improvement, although specific HR-QoL outcomes varied due to the differing safety profiles of the CDK4/6 inhibitors.
• Bone-Only Metastatic Breast Cancer: The addition of CDK4/6 inhibitors to ET improved PFS with an acceptable toxicity profile in patients with bone-only metastatic breast cancer.
• QTc Prolongation and Cardiovascular Risk: Ribociclib showed a significantly higher risk of QTc prolongation compared to Palbociclib, with a risk ratio (RR) of 3.12 for Ribociclib versus 1.51 for Palbociclib. Grade 3 QTc prolongations were observed exclusively with Ribociclib. Additionally, Abemaciclib + ET had a significantly lower risk of major adverse cardiovascular events (MACE) compared to Ribociclib + ET.
• Hematological and Gastrointestinal Toxicity: Palbociclib and Ribociclib exhibited higher rates of hematological toxicity, particularly neutropenia. In contrast, Abemaciclib was associated with higher rates of gastrointestinal toxicity, primarily diarrhea. Dalpiciclib also had a higher incidence of neutropenia compared to the other CDK4/6 inhibitors.
• Infection and Thromboembolism Risks: Patients receiving CDK4/6 inhibitors in combination with ET showed an increased risk of all-grade and grade 3 or higher infections, including urinary tract infections (UTIs) and febrile neutropenia, compared to ET alone. Additionally, a higher incidence of venous thromboembolism (VTE) was reported in patients treated with CDK4/6 inhibitors plus ET compared to ET alone.