Adjuvant CDK4/6 inhibitors combined with endocrine therapy in HR-positive, HER2-negative early breast cancer: A meta-analysis of randomized clinical trials
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
Affiliations
Hong-Fei Gao
Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, No.123 Huifu West, Yuexiu District, Guangzhou, 510080, Guangdong, China
Ying-Yi Lin
Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, No.123 Huifu West, Yuexiu District, Guangzhou, 510080, Guangdong, China; Shantou University Medical College, Shantou, 515041, Guangdong, China
Teng Zhu
Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, No.123 Huifu West, Yuexiu District, Guangzhou, 510080, Guangdong, China
Fei Ji
Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, No.123 Huifu West, Yuexiu District, Guangzhou, 510080, Guangdong, China
Liu-Lu Zhang
Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, No.123 Huifu West, Yuexiu District, Guangzhou, 510080, Guangdong, China
Ci-Qiu Yang
Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, No.123 Huifu West, Yuexiu District, Guangzhou, 510080, Guangdong, China
Mei Yang
Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, No.123 Huifu West, Yuexiu District, Guangzhou, 510080, Guangdong, China
Jie-Qing Li
Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, No.123 Huifu West, Yuexiu District, Guangzhou, 510080, Guangdong, China
Min-Yi Cheng
Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, No.123 Huifu West, Yuexiu District, Guangzhou, 510080, Guangdong, China
Kun Wang
Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, No.123 Huifu West, Yuexiu District, Guangzhou, 510080, Guangdong, China; Shantou University Medical College, Shantou, 515041, Guangdong, China; Corresponding author. Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, No.123 Huifu West, Yuexiu District, Guangzhou, 510080, Guangdong, China.
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.
