Adjuvant CDK4/6 inhibitors combined with endocrine therapy in HR-positive, HER2-negative early breast cancer: A meta-analysis of randomized clinical trials. (October 2021)

• Record Type: Journal Article
• Authors: Gao, Hong-Fei; Lin, Ying-Yi; Zhu, Teng; Ji, Fei; Zhang, Liu-Lu; Yang, Ci-Qiu; Yang, Mei; Li, Jie-Qing; Cheng, Min-Yi; Wang, Kun
• Is Part Of: Breast. Volume 59(2021)
• Page Start: 165
• Page End: 175
• Publication Date: 2021-10
• Subjects: CDK4/6 inhibitors -- Endocrine therapy -- Adjuvant -- Early breast cancer -- Meta-analysis; Breast -- Diseases -- Periodicals; Breast -- Tumors -- Periodicals; Breast -- Periodicals; Electronic journals; Periodicals; 616
• DOI: 10.1016/j.breast.2021.07.002
• Languages: English
• ISSNs: 0960-9776

Abstract

Abstract: Background: The benefit of adjuvant cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors with endocrine therapy (ET) in hormone receptor-positive, human epidermal growth factor 2 receptor-negative (HR+/HER2-) early breast cancer (EBC) is uncertain. Hence, we performed a meta-analysis to determine the efficacy and safety of adjuvant CDK4/6 inhibitors plus ET and to identify potential preferred subpopulations for this regimen. Methods: A literature search was conducted in PubMed, Embase, Cochrane databases up to Jan 15, 2021. Hazard ratios (HRs) for invasive disease-free survival (IDFS) and risk ratios (RRs) for grade 3/4 adverse events (AEs) and treatment discontinuation were extracted. Analysis with predefined subgroup variables was done. Trial sequential analysis (TSA) was performed to assess the conclusiveness of survival outcomes. Results: Three trials were eligible (N = 12647). Compared with ET, adjuvant CDK4/6 inhibitors with ET prolonged IDFS in patients with HR+/HER2- EBC (HR 0.87, 95% CI 0.76–0.98, p = 0.03, I 2 = 19%), with positive therapeutic responses observed in patients with N2/N3 nodal status (HR 0.83, 95% CI 0.71–0.97, p = 0.02, I 2 = 0%). None of the cumulative z-curves crossed the trial monitoring boundaries in TSA, and no reliable conclusion could be drawn. The combination treatment carried a higher risk of grade 3/4 AEs (RR 4.14, 95% CI 3.33–5.15, p < 0.00001) and an increase in treatment discontinuation due to AEs (RR 19.16, 95% CI 9.27–39.61, p < 0.00001). Conclusions: Adjuvant CDK4/6 inhibitors with ET might provide survival benefit in HR+/HER2- EBC. A statistically significantly improved IDFS was only observed in N2/N3 subgroup. However, overall evidence favoring the use of this combination regimen was inadequate. Highlights: Primary results from clinical trials investigating adjuvant CDK4/6 inhibitors were inconsistent. The meta-analysis demonstrated potential IDFS benefit of adjuvant CDK4/6 inhibitors with endocrine therapy in HR+/HER2-early breast cancer patients. A statistically significantly improved IDFS was observed in patients with N2/N3 nodal status. Overall evidence favoring the use of adjuvant CDK4/6 inhibitors remained inadequate.