| Objective: HER-2(human epidermal growth factor receptor 2)positive / HR(hormone receptor)positive advanced breast cancer is a subtype of breast cancer with unique biological behavior,and the optimal treatment for this subtype is still uncertain.At present,anti-Her-2 therapy combined with cytotoxic drugs is the first choice to alleviate disease progression and improve prognosis.However,there are results from large clinical trials showing that targeted combination endocrine agents can also achieve a survival advantage for patients with HER-2 + / HR + breast cancer.With the continuous development of medicine,molecular targeted drug combination therapy has become the mainstream of HER-2 + / HR + breast cancer treatment,and has good clinical efficacy.However,there are few studies directly comparing the efficacy of targeted combined endocrine therapy and targeted combined chemotherapy.In order to explore the difference of curative effect between targeted combination therapy in HER-2 + / HR + advanced breast cancer,it is necessary to make a systematic review of the research on HER-2 + / HR + advanced breast cancer so far,and compare the curative effect and safety,so as to provide reference for the selection of clinical treatment.Methods: Using the subject words and free words of this study and making the retrieval style and retrieval strategy according to Boolean logic,the Chinese knowledge network database,Wan fang medical database,Chinese biomedical literature database,VEP database,EMBASE,Pub Med,MEDLINE,the Cochrane Library and web of science were searched successively.The starting and ending time of the literature was 1987-oct-2020.Because some literatures analyzed HER-2+/HR+breast cancer as a subgroup,we collected randomized clinical trials on the efficacy and safety comparison of molecular targeted combined therapy in HER-2+ advanced breast and HER-2+/HR+ advanced breast cancer.Endnote software was used to screen the literature according to the pre-established inclusion and exclusion criteria,and the direct meta analysis and indirect mate analysis were carried out by using gemtc package and Stata software in Revman and R software.The safety and effectiveness of different treatment schemes were evaluated by HR(hazard ratio)and95% CI(95%,confidence interval)to evaluate PFS(progression free survival),and RR(relative risk degree)and 95% CI,or(odds ratio)and 95% CI.Results: Five original literatures were included in this study,including 695 patients with HER-2 + / HR + advanced breast cancer.All of them were RCTs(randomized controlled trials).Revman software was used to evaluate the risk of RCTs.The number of adverse events,OR(overall response rate),CBR(clinical benefit rate)were all counted.Direct Meta-Analysis: In terms of median PFS,molecular targeting combined with endocrinology was superior to endocrine monotherapy.The risk of recurrence and metastasis in the combination group was only 73% of that in the control group,with95% CI of 0.575-0.923,z = 2.63,P = 0.009 < 0.05,which was statistically significant.In terms of ORR and CBR,the molecular targeted combined with endocrine therapy group significantly increased ORR(RR = 2.149,95% CI: 1.415-3.266)and CBR(RR= 1.614,95% CI: 1.277-2.040).In terms of safety,the incidence rate of digestive system adverse events with molecular targeting combined endocrine group was relatively higher.The risk of diarrhea,diarrhea,vomiting and nausea increased more than 4.90 times,9.61 times,3.28 times and 2.02 times of the combination group,while the incidence of vomiting and nausea at grade 3 or 3 was not significantly higher than that of the control group.The incidence of fatigue in molecular targeted combined with endocrine group was 2.10 times higher than that in endocrine group,but there was no significant difference in the incidence of fatigue ≥ 3 grade between molecular targeted combined with endocrine group and endocrine group.For the overall level ≥ 3 adverse events,there was no significant difference in the incidence of molecular targeting combined with endocrine level ≥ 3 adverse events between the two groups(P > 0.05).Indirect Meta-Analysis: In terms of median PFS,molecular targeted combined with endocrine is better than endocrine monotherapy,but there is no significant difference between molecular targeted combined therapy and between molecular targeted combined chemotherapy and endocrine.In terms of ORR,molecular targeted combined with endocrine therapy is better than endocrine therapy.There is no significant difference between molecular targeted combined therapy and molecular targeted combined chemotherapy compared with endocrine therapy.In terms of CBR,molecular targeted combined with endocrine therapy is better than molecular targeted combined with chemotherapy,and better than endocrine therapy.There is no significant difference between molecular targeted combined with chemotherapy and endocrine therapy.In terms of safety,there was no significant difference in the incidence of adverse events between the two groups,but the incidence of adverse events in the molecular targeted combined with endocrine group was higher than that in the endocrine group.Conclusion: 1.In terms of PFS and ORR,compared with endocrine monotherapy,the risk of recurrence and metastasis of HER-2 + / HR + advanced breast cancer patients is reduced,and there is no significant difference between molecular targeted therapy and endocrine monotherapy.2.In terms of CBR,molecular targeted combined with endocrine is better than molecular targeted combined with chemotherapy,and molecular targeted combined with endocrine is better than endocrine.There is no statistical difference between molecular targeted combined with chemotherapy and endocrine.3.In terms of safety,the probability of grade ≥ 3 adverse events was not significantly different among the three treatment arms,and the incidence of adverse events was similar between targeted combination therapy arms but higher than the endocrine arm. |
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