Efficacy and Safety of Ribociclib Plus Endocrine Therapy Versus Endocrine Therapy Alone in HR-Positive/HER2-Negative...

Recent trials of ribociclib, a cyclin-dependent kinase inhibitor, have shown promising results in patients with hormone receptor-positive (HR+)/HER2-negative (HER2-) breast cancer. This meta-analysis evaluates the efficacy and safety of combining ribociclib with endocrine therapy (ET) versus ET alone in this patient population.

A comprehensive search of PubMed, Embase, CENTRAL, Scopus, and Web of Science (up to July 2024, no language restrictions) identified randomized controlled trials (RCTs) comparing endocrine therapy (ET) with and without ribociclib for HR+/HER2- breast cancer. Bias was assessed using Cochrane's Risk of Bias tool. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and odds ratios (ORs) for Grade III + adverse effects (neutropenia, hepatobiliary toxicity, QT prolongation, and interstitial pneumonitis) were calculated with 95% confidence intervals (CI). A random-effects model accounted for heterogeneity (I² statistic). The protocol was registered in PROSPERO (CRD42024558512).

The meta-analysis of 5 RCTs (7286 participants) showed ribociclib plus ET significantly improved OS (HR 0.76, 95% CI 0.68-0.85, P < .001) and PFS (HR 0.57, 95% CI 0.51-0.64, P < .001) compared with ET alone. Grade III + adverse effects of special interest that were more common with ribociclib plus ET include neutropenia (OR 75.76, 95% CI 35.23-162.93, P < .001), hepatobiliary toxicity (OR 2.54, 95% CI 1.32-4.90, P = .005), and QT prolongation (OR 2.95, 95% CI 1.69-5.16, P < .001). The rare grade III + interstitial pneumonitis events (OR 3.36, 95% CI 0.56-20.07, P = .18) also warrant ongoing vigilance.

Ribociclib combined with ET improves OS and PFS but is associated with higher rates of adverse effects, compared with ET alone, highlighting the need for careful monitoring and management.

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