Toxicity profile of cyclin-dependent kinase inhibitors in real-time clinical practice

Background. Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are a standard of care for ER-positive/HER2-negative metastatic breast cancer (MBC), yet real-world safety may differ from randomized controlled trials (RCTs).
Objective. To assess the safety of palbociclib and ribociclib combined with endocrine therapy in routine clinical practice.
Methods. Prospective, open-label, single-center, non-randomized study including 815 patients treated between April 2020 and October 2023. Palbociclib cohort: n=365 (125 mg QD, 21/7); ribociclib cohort: n=450 (600 mg QD, 21/7). Adverse events (AEs) were graded by CTCAE v5.0; standard statistics with p<0.05.
Results. Any-grade AEs occurred in 33.4% (palbociclib) and 24.0% (ribociclib). Toxicity spectra differed: palbociclib was associated mainly with hematologic AEs—neutropenia in 112/365 (30.7%), including grade 3–4 in 37/365 (10.1%); febrile neutropenia in 1/365 (0.3%). Ribociclib showed predominantly non-hematologic AEs — asthenia in 34/450 (7.6%) (mostly grade ≤2); ALT/AST elevations in 16/450 (3.6%); QT interval prolongation in 2/450 (0.4%). Diarrhea and rash were uncommon in both cohorts. Dose reductions implemented for toxicity did not compromise progression-free survival in within-group comparisons.
Conclusions. In real-world practice, CDK4/6 inhibitors demonstrate favorable tolerability with predictable, distinct toxicity patterns (hematologic with palbociclib; mainly non-hematologic with ribociclib), supporting individualized drug selection and safety monitoring strategies.

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