CDK4/6 Inhibitors Combined With Endocrine Therapy For Advanced Breast Cancer Clinical Study On Efficacy And Safety

Objective: This study was retrospectively analyzed.To summarize the clinical efficacy of Cyclin-Dependent Kinase 4 and 6 inhibitor(CDK4/6i)combined with Endocrine Therapy(ET)in patients with Hormone Receptor positive(HR+)/ Human epidermal growth factor receptor 2-negative(HER2-)advanced or progressive breast cancer and adverse events with an incidence of ≥ 15%.A meta-analysis was conducted to find the absolute beneficiary population and predictive biomarkers of CDK4/6 inhibitors,and to provide theoretical basis and practical cases for subsequent clinical medication by standardizing the classification,classification and management of adverse events.Methods: The clinical data of 90 patients with advanced or progressive breast cancer treated with CDK4/6 inhibitors combined with endocrine therapy from October 2020 to December 2022 were retrospectively collected.The subjects included in this study were all female,ECOG≤2,HR+/HER2-molecular typing by puncture or surgical immunohistochemistry,and recurrence or metastasis after treatment by imaging or pathological evaluation.Patients with recurrent or metastatic breast cancer after treatment or newly diagnosed advanced breast cancer were all in stage IV.According to the differences in clinical application of CDK4/6 inhibitors,they were divided into two treatment subgroups : Abemaciclib and Palbociclib.A stratified analysis of clinical baseline characteristics and treatment experience was performed in the overall population and between the two subgroups to find the beneficiaries of CDK4/6inhibitors and predict biomarkers.Data were statistically analyzed using SPSS22.0.Disease control rate(DCR)was statistically inferred using chi-square analysis.Log-Rank test was performed for progression-free survival(PFS)and adverse events with an incidence of ≥15 %.Finally,COX regression analysis was used to infer the prognostic factors affecting PFS using CDK4/6 inhibitors.The significance test level of statistical analysis was α=0.05.Results: A total of 90 subjects were included in the study.The overall population DCR : 73.3 %,median progression-free survival : 10 months,median overall survival :9.5 months.There were statistically significant differences in the efficacy of bone metastasis,liver metastasis and estrogen receptor(ER)level stratification in the overall population,and ER level was an independent protective factor for PFS.A total of 35 patients were included in the subgroup of Palbociclib combined with endocrine therapy.DCR : 62.9 %,median progression-free survival : 9.5 months;there were statistically significant differences in the stratification of treatment lines,previous chemotherapy effectiveness,ER level,bone metastasis and liver metastasis,among which liver metastasis was an independent risk factor for PFS in the Palbociclib group.There were 55 patients in the subgroup of Abemaciclib combined with endocrine therapy,DCR : 80.0 %,median progression-free survival : 9 months,only liver metastasis was related to the short-term efficacy,and the other baseline characteristics were not statistically significant with the short-term and long-term efficacy.In the course of treatment,72 patients(80.0%)had at least one adverse event.Bone marrow suppression,diarrhea,abnormal liver function,and stomatitis were adverse events with high incidence.All adverse events were concentrated in grades 1and 2,and most of them were controllable.The incidence of bone marrow suppression was the highest in the Palbociclib group,while diarrhea and bone marrow suppression were the highest incidence of adverse events in the Abemaciclib group.In addition,we performed a Log-Rank test on adverse events with an incidence of ≥15%,and the results suggested that bone marrow suppression was associated with the prognosis of Palbociclib.Conclusion:(1)CDK4 / 6 inhibitors combined with endocrine therapy have good clinical efficacy in patients with advanced breast cancer.(2)The adverse events occurred were concentrated in grade 1 and 2,with high safety.(3)The level of ER may be an independent protective factor for PFS in the overall population,while liver metastasis may be an independent risk factor for PFS in the Palbociclib group.