Safety and efficacy profile of cyclin-dependent kinases 4/6 inhibitor palbociclib in cancer therapy: A meta-analysis of clinical trials.

BACKGROUND: Palbociclib is a small-molecule, cyclin-dependent kinase 4 and 6 inhibitor, which prevents phosphorylation of the retinoblastoma (Rb) protein and inhibits cell-cycle progression from G1 to S phase. We performed this meta-analysis to estimate the safety and efficacy of palbociclib in cancer patients from clinical trials.

METHODS: PubMed and EMBASE were searched for eligible studies. Adverse events (AE) of grade ≥3 and all-grade (1-5) were extracted to calculate event rates. Odds ratios (ORs) with 95% confidence interval (CI) were calculated to estimate the safety of palbociclib in endocrine treatment-combined studies. A fixed effects model was used when homogeneity was low (I2  ≤ 50%). A random effects model was adopted when there was a significant heterogeneity (I2  > 50%). For efficacy endpoints, hazard ratio (HR) and 95% CI for progression-free survival (PFS) or overall survival (OS) were extracted and analyzed.

RESULTS: Nine clinical trials representing 1534 patients were identified. The most frequently observed all-grade adverse events (AEs) in patients treated with palbociclib were neutropenia (event rate: 68.1%), leukopenia (51.7%), fatigue (35.9%), anemia (34.7%), and thrombocytopenia (30.9%). The most common grade 3 or more toxicities were neutropenia (51.6%), leukopenia (29.4%), and thrombocytopenia (7.5%). Hematologic adverse events had high occurrence in the palbociclib group. The pooled analysis of survival outcomes suggested that palbociclib produced clinical benefits in breast cancers and Rb-positive tumors. More specifically, palbociclib was associated with significant improvement of PFS (HR: 0.518, 95% CI: 0.444-0.604) in the treatment of ER-positive and HER2-negative breast cancer.

CONCLUSIONS: Hematologic adverse events were common in palbociclib-treated cancer patients. Since palbociclib produced a higher PFS rate with a low serious complication rate, it can be a promising novel target therapy drug for treating ER-positive and HER2-negative breast cancer.