| Objective:The efficacy and safety of molecular targeted drugs combined with endocrine therapy for breast cancer patients with hormone-receptor-positive(hormone receptor,HR)breast cancer were systematically evaluated.Method:According to keywords,we searched the English and Chinese database.We collected the randomized controlled trials which met the inclusion criteria,and evaluated their quality by using the Cochrane manual standard.The data were extracted,and Meta analysis was carried out in the included studies using the statistical software Stata12.0 and RevMan5.3.Result:A total of 19 randomized controlled trials(randomized controlled trials,RCTs)were included in this study.According to Cochrane quality evaluation,the results were 3 articles with low bias risks,3 articles with high bias risks and 13 articles with unknown risks.The results of Meta-analysis are as follows:1.Compared with endocrine therapy alone,the effectiveness of molecular targeted drugs combined with endocrine therapy drugs is systematically evaluated in HR positive breast cancer patients.The median progression-free survival(progression-free survival,PFS)was systematically evaluated as the primary endpoint.Compared with the single group,the risk of tumor recurrence or metastasis was reduced by 42%.CDK4/6 inhibitor,mTOR inhibitor,PI3 K inhibitor and Anti-HER-2 agents was used respectively in combination with endocrine therapy.Compared with the single use group,the risk of tumor recurrence or metastasis in combination group was decreased respectively by48%,54%,23% and 23%.The confidence intervals(Confidence Interval,CI)did not contain 1,and the differences were statistically significant.The overall survival(overall survival,OS),the clinical benefit rate(clinical benefit rate,CBR)and the objective response rate(objective response rate,ORR)were used as the secondary end point,and they were systematically evaluated.Compared with the single use group,the risk of death in the combined group was decreased by 19%.CI did not contain 1,and the difference was statistically significant.But there is no significant difference in CBR and ORR.2.Compared with endocrine therapy alone,the safety of molecular targeted drugs combined with endocrine therapy drugs is systematically evaluated in HR positive breast cancer patients.2.1 Effect on blood systemCompared with the single group,the risk of neutropenia,leukopenia and anemia in the combined group was increased respectively by 1450 %,655 %,269 % and 2572%.The risk of grade 3-4 in the combined group was increased respectively by 4235%,3253 %,174 % and 943 %.The difference was statistically significant(P< 0.05).2.2 Effect on digestive systemCompared with the single group,the risk of vomiting,decreased appetite,nausea,diarrhea,abdominal pain and constipation in the combined group was increased respectively by 54%,96%,29%,106%,73% and 12%,the risk of grade 3-4decreased appetite and diarrhoea in the combined group was increased respectively by 164% and 437%,and the difference was statistically significant(P<0.05).There was no significant difference in the risk of grade 3-4 vomiting,nausea,abdominal pain and constipation.(P>0.05).2.3 Effects on respiratory systemCompared with the single group,the risk of cough and dyspnea in the combined group was increased respectively by 33% and 35%.The difference was statistically significant(P<0.05).There was no significant difference in the risk of upper respiratory tract infection.There was no significant difference in the risk of grade 3-4cough,dyspnea,and upper respiratory tract infection(P>0.05).2.4 Effects on neural systemCompared with the single group,the risk of insomnia,headache and dizziness in the combined group was increased respectively by 36%,25% and 56%,and thedifference was statistically significant(P<0.05).There was no significant difference in the risk of grade 3-4(P>0.05).2.5 Effects on liver and kidney functionCompared with the single group,the risk of increased alanine aminotransferase and aspertate aminotransferase in the combined group was increased respectively by212% and 172%.The risk of grade 3-4 in the combined was increased respectively by336% and 203%.The risk of elevated serum creatinine in the combined was increased by 826%,and the difference was statistically significant(P<0.05).There was no significant difference in the risk of grade 3-4 elevated serum creatinine and serum bilirubin(P>0.05).2.6 Effects on blood lipids,blood glucose and blood pressureCompared with the single group,the risk of hyperglycemia,hypertension and hyperlipidemia in the combined group was increased respectively by 291%,125%and116%,and the risk of grade 3-4 hyperglycemia in the combined was increased by426%,and the difference was statistically significant(P<0.05).There was no significant difference in the risk of grade 3-4 hypertension and hyperlipidemia(P>0.05).2.7 Effect on achingCompared with the single group,the risk of arthralgia and grade 3-4 limb pain in the combined group was decreased respectively by 9% and 76%,while the risk of bone pain in the combined group was increased by 105%,and the difference was statistically significant(P<0.05).There was no significant difference in the risk of back pain,limb pain,and there was no significant difference in the risk of grade 3-4arthralgia,bone pain and back pain(P>0.05).2.8 Effect on skinCompared with the single group,the risk of rash,pruritus and dry skin in the combined group was increased respectively by 239%,115% and 204%.The risk of grade 3-4 rash and pruritus in the combined group was increased respectively by979% and 376%,and the difference was statistically significant(P<0.05).There was no significant difference in the risk of grade 3-4 skin dry(P>0.05).2.9 OthersCompared with the single group,the risk of stomatitis,fatigue,asthenia,fever,infection,alopecia and weight loss in the combined group was increased respectively by 265%,34%,75%,75%,47%,135%,198% and 153%,and the risk of 3-4 grade stomatitis,fatigue and asthenia in the combined group was increased 529%,198%and 134%.The risk of hot flush in the combined group was decreased by 19%.The difference was statistically significant(P<0.05).There was no significant difference in risk of grade 3-4 hot flush,fever,infection and weight loss(P>0.05).Conclusion:1.The effectiveness of therapeutic drugsHR positive breast cancer patients were treated with endocrine combined molecular targeted therapy group compared with single endocrine therapy group:(1)The median PFS and OS were significantly prolonged;(2)Using CDK4/6,mTOR,PI3 K inhibitors and Anti-HER-2 drugs could prolong the median PFS of patients.2.The incidence of adverse therapeutic drug reactions.Compared with the single endocrine therapy,the incidence of adverse reactions in patients with HR positive breast cancer treated with endocrine combined molecular targeted therapy was inceased significantly.The increased adverse reactions are as follows:(1)Blood system: neutrophilic,leukocytopenia,anemia and thrombocytopenia;(2)Digestive system: vomiting,decreased appetite,nausea,diarrhea,abdominal pain and constipation;(3)Respiratory system: cough and dyspnea;(4)Neural system: insomnia,headache and dizziness;(5)The function of liver and kidney: elevated alanine aminotransferase,aspartate aminotransferase and serum creatinine;(6)Blood lipids,blood glucose and blood pressure: hyperglycemia,hypertension and hyperlipidemia;(7)Bone pain;(8)Skin: rash,pruritus and dry skin;(9)Others: stomatitis,fatigue,fatigue,fever,infection,alopecia and weight loss.Compared with the single endocrine therapy,the incidence of adverse reactions in patients with HR positive breast cancer treated with endocrine combined molecular targeted therapy was deceased significantly.The decreased adverse reactions are as follows: Arthralgia,limb pain and hot flash. |
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