Hehui Fang1, Doudou Huang1, Fang Yang1, Xiaoxiang Guan2. 1. Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, China. 2. Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, China. xguan@nju.edu.cn.
Abstract
PURPOSE: Cyclin D/cyclin-dependent kinase 4/6 (CDK4/6) complex inhibitors have recently been proven effective when combined with endocrine therapy in clinical trials. However, the clinical benefit from CDK4/6 inhibitor varied from different patients. In order to optimize the clinical application of CDK4/6 inhibitors, this review focuses on the potential biomarkers applicable to identify patients who will benefit the most from CDK4/6 inhibition. METHODS: We have summarized the clinical trials about addition of CDK4/6 inhibitors to endocrine therapy and reviewed literature currently available on the potential biomarkers in predicting efficacy of CDK4/6 inhibitors. The primary objective was to determine the predictors. The secondary objective was to optimize the combination therapeutics for patients with estrogen receptor (ER)-positive breast cancer. RESULTS: We reviewed clinical trials on antiestrogen agents combined with the CDK4/6 inhibitor (Palbociclib, Ribociclib, or Abemaciclib) in ER-positive breast cancer. It was confirmed that the addition of CDK4/6 inhibitors was associated with an improved efficacy. More importantly, we discussed potential biomarkers for identifying the subpopulations of breast cancer patients who would derive the greatest benefit from CDK4/6 inhibitors. CONCLUSIONS: We have found that although CDK4/6 inhibitors combined with endocrine therapy were potent, the toxicity and financial burden also increased. To maximize the effect of the combinations and select patients that best response to such combinations, further experiments and trials are expected to confirm these molecules as reliable biomarkers.
PURPOSE: Cyclin D/cyclin-dependent kinase 4/6 (CDK4/6) complex inhibitors have recently been proven effective when combined with endocrine therapy in clinical trials. However, the clinical benefit from CDK4/6 inhibitor varied from different patients. In order to optimize the clinical application of CDK4/6 inhibitors, this review focuses on the potential biomarkers applicable to identify patients who will benefit the most from CDK4/6 inhibition. METHODS: We have summarized the clinical trials about addition of CDK4/6 inhibitors to endocrine therapy and reviewed literature currently available on the potential biomarkers in predicting efficacy of CDK4/6 inhibitors. The primary objective was to determine the predictors. The secondary objective was to optimize the combination therapeutics for patients with estrogen receptor (ER)-positive breast cancer. RESULTS: We reviewed clinical trials on antiestrogen agents combined with the CDK4/6 inhibitor (Palbociclib, Ribociclib, or Abemaciclib) in ER-positive breast cancer. It was confirmed that the addition of CDK4/6 inhibitors was associated with an improved efficacy. More importantly, we discussed potential biomarkers for identifying the subpopulations of breast cancerpatients who would derive the greatest benefit from CDK4/6 inhibitors. CONCLUSIONS: We have found that although CDK4/6 inhibitors combined with endocrine therapy were potent, the toxicity and financial burden also increased. To maximize the effect of the combinations and select patients that best response to such combinations, further experiments and trials are expected to confirm these molecules as reliable biomarkers.
Authors: Sara A Hurvitz; Miguel Martin; Michael F Press; David Chan; María Fernandez-Abad; Edgar Petru; Regan Rostorfer; Valentina Guarneri; Chiun-Sheng Huang; Susana Barriga; Sameera Wijayawardana; Manisha Brahmachary; Philip J Ebert; Anwar Hossain; Jiangang Liu; Adam Abel; Amit Aggarwal; Valerie M Jansen; Dennis J Slamon Journal: Clin Cancer Res Date: 2019-10-15 Impact factor: 12.531