Efficacy and safety of neoadjuvant therapy for HR-positive/HER2-negative early breast cancer: a Bayesian network meta-analysis

Neoadjuvant treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer is controversial and requires a comprehensive analysis for optimal therapy assessment. Therefore, a two-step Bayesian network meta-analysis (NMA) was performed to compare the efficacy and safety of different neoadjuvant regimens. Phase II/III randomized clinical trials comparing various neoadjuvant therapies for HR+/HER2- breast cancer were included. NMA and pairwise meta-analyses were conducted using Stata (version 14), R (version 4.2.3), and Review Manager 5.4. Twenty-eight studies (5,625 patients) were eligible. NMA of objective response rate (ORR) indicated the highest SUCRA for chemotherapy (CT) and chemotherapy with anthracycline (CT(A)). Pathologic complete response (PCR) NMA demonstrated significant PCR improvement with chemotherapy regimens containing programmed cell death protein-1 and programmed cell death ligand-1 inhibitors (PD-1i/PD-L1i) and poly ADP-ribose polymerase inhibitors (PARPi). Combined analysis considering both the ORR and safety highlighted CT(A)’s efficacy and toxicity balance. CT(A) and CT showed improved ORR compared with alternative regimens. CT(A) combined with PD-1/PD-L1 or PARP inhibitors significantly increased PCR rates. Comprehensive assessment of both ORR and safety indicated that CT(A) represents an optimal neoadjuvant therapy for HR+/HER2- breast cancer, whereas AI + CDK4/6 inhibitors rank solely behind chemotherapy. PROSPERO Registration: CRD42024538948. International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) registration number INPLASY202440092.

针对激素受体阳性/人表皮生长因子受体2阴性（HR+/HER2-，hormone receptor-positive/human epidermal growth factor receptor 2-negative）乳腺癌的新辅助治疗尚存争议，亟需开展全面分析以优化治疗方案的评估。为此，本研究采用两步法贝叶斯网络Meta分析（Bayesian network meta-analysis, NMA）对比不同新辅助治疗方案的疗效与安全性。本研究纳入对比各类新辅助疗法治疗HR+/HER2-乳腺癌的II/III期随机临床试验。采用Stata（14版）、R（4.2.3版）及Review Manager 5.4软件开展网络Meta分析及配对Meta分析。最终纳入28项研究，共计5625例患者。客观缓解率（objective response rate, ORR）的网络Meta分析结果显示，化疗（chemotherapy, CT）及含蒽环类化疗（chemotherapy with anthracycline, CT(A)）的累积排序概率图下面积（SUCRA）最高。病理完全缓解（Pathologic complete response, PCR）的网络Meta分析表明，含程序性死亡蛋白-1及程序性死亡配体-1抑制剂（PD-1i/PD-L1i）与多聚ADP核糖聚合酶抑制剂（poly ADP-ribose polymerase inhibitors, PARPi）的化疗方案可显著提升病理完全缓解率。同时结合客观缓解率与安全性的综合分析显示，CT(A)的疗效与毒性平衡表现最优。相较于其他备选方案，CT(A)与单纯化疗的客观缓解率更优。CT(A)联合PD-1/PD-L1抑制剂或PARP抑制剂可显著提高病理完全缓解率。综合客观缓解率与安全性评估结果表明，CT(A)是HR+/HER2-乳腺癌的最优新辅助治疗方案，而芳香化酶抑制剂（aromatase inhibitor, AI）联合CDK4/6抑制剂的疗效仅次于化疗方案。本研究已在PROSPERO注册平台完成注册，注册号为CRD42024538948；同时在国际系统评价与Meta分析方案注册平台（International Platform of Registered Systematic Review and Meta-Analysis Protocols, INPLASY）完成注册，注册号为INPLASY202440092。