Palbociclib plus endocrine therapy or GnRH analogs versus capecitabine or placebo for HR+/HER2- metastatic breast cancer: A systematic review and meta-analysis.

Abstract

e13018 Background: Breast cancer, particularly the HR+/HER2- subtype, remains a major global health concern. Palbociclib, a CDK4/6 inhibitor, has demonstrated effectiveness when combined with endocrine therapy against hormone receptor-positive, human epidermal growth factor 2-negative (HR+/HER2-) metastatic breast cancer. Compared to chemotherapy alone, palbociclib plus endocrine therapy is more effective in improving patient outcomes and progression-free survival for patients with HR+/HER2-metastatic breast cancer. Methods: A systematic review and meta-analysis were conducted using PRISMA guidelines. From inception until December 2024, a thorough literature search was conducted using PubMed, Scopus, Cochrane, and Embase databases. Five RCTs were identified comparing the efficacy of palbociclib plus endocrine therapy and capecitabine or placebo in patients with HR+/HER2 metastatic breast cancer. Outcomes assessed included OS, PFS, ORR, RD, and AE/SAE using RevMan 5.4. Quality assessment was done using RoB 2.0. Results: A pooled analysis of 5 studies, including 2306 patients with a mean age of 53.3 years (SD: 9.86 years), showed that palbociclib plus ET had improved ORR with HR of 0.77 (95% CI: 0.60, 0.99) with no heterogeneity (I2 = 0%) when compared to capecitabine or placebo. Palbociclib plus et al. so demonstrated improved PFS with HR of 0.75 (95% CI: 0.67, 0.84) but with significant heterogeneity (I2 = 83%, P < 0.0001). Palbociclib plus ET was found inferior to capecitabine or placebo when assessing the risk of leukopenia, neutropenia, and thrombocytopenia with RR of 7.7 (95% CI: 4.85, 12.34), 11.24 (95% CI: 4.09, 30.89), and 5.78 (95% CI: 2.85, 11.70), respectively. Furthermore, palbociclib plus ET demonstrated no statistically significant superiority to capecitabine or placebo in terms of overall MS and median RD, exhibiting HR of 0.88 (95% CI: 0.76, 1.03) and 0.73 (95% CI: 0.47, 1.11) respectively. Conclusions: Palbociclib, when used in combination with ET, showed improvement in PFS and ORR in HR+/HER2- metastatic breast cancer patients as compared to capecitabine or placebo but demonstrated no superiority in terms of overall MS and median RD. Future research directions should explore the long-term efficacy and safety of palbociclib plus ET for the treatment of metastatic breast cancer in diverse clinical settings. This review offers insights for clinical decision-making within the dynamic and advancing field of breast cancer treatment.