Dai Youran, Ruan Tianyin, Yang Wenhui, Liu Shan, Chen Jiahao, Fang Yingying, Li Qiushuang
The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China.
Institute of Hepatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Clin Med Insights Oncol. 2024 Dec 23;18:11795549241308072. doi: 10.1177/11795549241308072. eCollection 2024.
Triple negative breast cancer (TNBC) is a deadly subtype of breast cancer with limited treatment options. Currently, programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors have become the first choice for breast cancer immunotherapies. Despite paclitaxel being considered a cornerstone drug in breast cancer treatment, the effectiveness, safety, and optimal drug selection for its combination with PD-1/PD-L1 inhibitors remain uncertain.
We conducted a systematic review and network meta-analysis, performing a comprehensive literature search across PubMed, Embase, and the Cochrane Library from the inception of each database through May 18, 2024. Selected trials were those that assessed the efficacy and safety of paclitaxel-based PD-1/PD-L1 therapies for the treatment of TNBC. The primary endpoint assessed was overall survival (OS), while secondary outcomes included progression-free survival (PFS), adverse events (AEs), overall response rate (ORR), and Pathological complete response (pCR). This study is registered in PROSPERO under registration number CRD42023429651.
A total of 8 RCTs meeting our eligibility criteria were included, involving 4626 patients who received either Paclitaxel (Paclitaxel-placebo/chemotherapy) or a combination of durvalumab, pembrolizumab, atezolizumab, toripalimab with paclitaxel. The pooled results demonstrated that Durvalumab combined with Paclitaxel significantly reduced the hazard ratio for OS (surface under the cumulative ranking [SUCRA]: 91.05%) and PFS compared with Paclitaxel alone (SUCRA: 83.52%). Additionally, Durvalumab plus Paclitaxel significantly improved the ORR compared with Paclitaxel (odds ratio [OR]: 2.30; 95% credible interval [CrI]: 1.10-5.20). For safety outcomes, Atezolizumab plus Paclitaxel showed a favorable profile in AEs, with no significant differences observed between groups. In the pCR study, Pembrolizumab plus Paclitaxel was the most effective treatment option (SUCRA: 81.85%).
When combined with paclitaxel, PD-1/PD-L1 inhibitors exhibit a favorable survival benefit. The combination of Durvalumab and paclitaxel represents the optimal treatment option. In the future, attention should be paid to the TNBC subtypes and drug dosage, as these factors may help to design personalized TNBC treatment programs.
三阴性乳腺癌（TNBC）是一种致命的乳腺癌亚型，治疗选择有限。目前，程序性死亡1（PD-1）/程序性死亡配体1（PD-L1）抑制剂已成为乳腺癌免疫治疗的首选。尽管紫杉醇被认为是乳腺癌治疗的基石药物，但其与PD-1/PD-L1抑制剂联合使用的有效性、安全性和最佳药物选择仍不确定。
我们进行了一项系统评价和网络荟萃分析，从每个数据库建立至2024年5月18日，在PubMed、Embase和Cochrane图书馆进行了全面的文献检索。入选的试验是那些评估基于紫杉醇的PD-1/PD-L1疗法治疗TNBC的疗效和安全性的试验。评估的主要终点是总生存期（OS），次要结局包括无进展生存期（PFS）、不良事件（AE）、总缓解率（ORR）和病理完全缓解（pCR）。本研究已在PROSPERO注册，注册号为CRD42023429651。
共纳入8项符合我们纳入标准的随机对照试验，涉及4626例接受紫杉醇（紫杉醇-安慰剂/化疗）或度伐利尤单抗、帕博利珠单抗、阿替利珠单抗、托瑞帕利单抗与紫杉醇联合治疗的患者。汇总结果表明，与单独使用紫杉醇相比，度伐利尤单抗联合紫杉醇显著降低了OS（累积排名曲线下面积[SUCRA]：91.05%）和PFS的风险比（SUCRA：83.52%）。此外，与紫杉醇相比，度伐利尤单抗加紫杉醇显著提高了ORR（优势比[OR]：2.30；95%可信区间[CrI]：1.10-5.20）。对于安全性结局，阿替利珠单抗加紫杉醇在不良事件方面表现良好，各治疗组之间未观察到显著差异。在pCR研究中，帕博利珠单抗加紫杉醇是最有效的治疗选择（SUCRA：81.85%）。
当与紫杉醇联合使用时，PD-1/PD-L1抑制剂显示出良好的生存获益。度伐利尤单抗和紫杉醇的联合是最佳治疗选择。未来，应关注TNBC亚型和药物剂量，因为这些因素可能有助于设计个性化的TNBC治疗方案。
