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 (I (2) ≤ 50%). A random effects model was adopted when there was a significant heterogeneity (I (2) > 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.