by
Hong-Fei Gao, Ying-Yi Lin, Teng Zhu, Fei Ji, Liu-Lu Zhang, Ci-Qiu Yang, Mei
Yang, Jie-Qing Li, Min-Yi Cheng, Kun Wang
The Breast: VOLUME 59, P165-175, OCTOBER
01, 2021
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, I2 = 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, I2 = 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.
