Yuan Ye, Liu Xumei, Xu Gaifeng, Zhang Ji, Chen Li, Long Xin
Sichuan Integrative Medicine Hospital, China.
Chengdu Anticancer Bioscience, China.
Cancer Treat Rev. 2025 Mar;134:102901. doi: 10.1016/j.ctrv.2025.102901. Epub 2025 Feb 17.
HER2-positive breast cancer is an aggressive subtype that benefits from targeted therapies. Some studies have shown that pyrotinib (P) plus trastuzumab (H) has a good efficacy against early or locally advanced HER2-positive breast cancer. However, there is still no systematic review and meta-analysis supporting the efficacy and safety of pyrotinib plus trastuzumab versus standard regimens in the neoadjuvant treatment of early or locally advanced breast cancer. This study is the first systematic review and meta-analysis to compare the efficacy and safety of pyrotinib combined with trastuzumab versus trastuzumab combined with pertuzumab (Per) and trastuzumab monotherapy in the neoadjuvant treatment of HER2-positive breast cancer.
We conducted a systematic literature search in PubMed, Embase, the Cochrane Library, CNKI, Wan Fang and VIP databases for relevant studies published up to August 30th, 2024. RCTs, cohort studies and retrospective studies with HER2-positive breast cancer patients who had not received breast cancer-related treatments previously were included. Treatment of P + H, H or Per + H arms with chemotherapy combined with pyrotinib plus trastuzumab, trastuzumab or pertuzumab plus trastuzumab as neoadjuvant treatment. The primary outcome was the total pathological complete response (tpCR), and secondary outcomes included breast pathological complete response (bpCR), ORR, DCR, and grade III/IV AEs. The quality of evidence was assessed using the GRADE.
A total of nine studies (4 RCTs, 1 prospective cohort study and 4 retrospective analysis) involving 1745 patients were included. The P + H arm showed no significant difference in tpCR compared to Per + H (RR: 0.94, 95 % CI: 0.80-1.11, p = 0.46) but demonstrated a significant improvement in tpCR over trastuzumab monotherapy (RR: 1.83, 95 % CI: 1.56-2.15, p < 0.001). This finding was further confirmed in meta-analysis of RCTs (RR: 1.87, 95 % CI: 1.42-2.47, p < 0.001). The P + H arm had a higher incidence of grade III/IV diarrhea (RR: 10.54, 95 % CI: 5.96-18.63, p < 0.001) but similar rates of other AEs compared to the H arm. The evidence quality for tpCR (P + H vs. H, RCT) was high, and that for tpCR (P + H vs. H) was moderate, while that for tpCR (P + H vs. Per + H) was low.
Pyrotinib combined with trastuzumab may offer an effective neoadjuvant treatment option for HER2-positive breast cancer, with a superior efficacy over trastuzumab alone. However, pyrotinib plus trastuzumab did not show better efficacy compared with Per + H. Pyrotinib plus trastuzumab was associated with more diarrhrea than trastuzumab monotherapy. In addition, P + H is less cost-effective compared with the combination of Per + H.
人表皮生长因子受体2（HER2）阳性乳腺癌是一种侵袭性亚型，可从靶向治疗中获益。一些研究表明，吡咯替尼（P）联合曲妥珠单抗（H）对早期或局部晚期HER2阳性乳腺癌具有良好疗效。然而，尚无系统评价和荟萃分析支持吡咯替尼联合曲妥珠单抗与标准方案在早期或局部晚期乳腺癌新辅助治疗中的疗效和安全性。本研究是第一项比较吡咯替尼联合曲妥珠单抗与曲妥珠单抗联合帕妥珠单抗（Per）及曲妥珠单抗单药在HER2阳性乳腺癌新辅助治疗中疗效和安全性的系统评价和荟萃分析。
我们在PubMed、Embase、Cochrane图书馆、中国知网、万方和维普数据库中进行了系统的文献检索，纳入截至2024年8月30日发表的相关研究。纳入未曾接受过乳腺癌相关治疗的HER2阳性乳腺癌患者的随机对照试验（RCT）、队列研究和回顾性研究。将吡咯替尼联合曲妥珠单抗（P + H）、曲妥珠单抗（H）或帕妥珠单抗联合曲妥珠单抗（Per + H）作为新辅助治疗与化疗联合应用。主要结局为总病理完全缓解（tpCR），次要结局包括乳腺病理完全缓解（bpCR）、客观缓解率（ORR）、疾病控制率（DCR）和Ⅲ/Ⅳ级不良事件（AE）。采用GRADE评估证据质量。
共纳入9项研究（4项RCT、1项前瞻性队列研究和4项回顾性分析），涉及1745例患者。与Per + H相比，P + H组在tpCR方面无显著差异（风险比[RR]：0.94，95%置信区间[CI]：0.80 - 1.11，p = 0.46），但与曲妥珠单抗单药治疗相比，tpCR有显著改善（RR：1.83，95% CI：1.56 - 2.15，p < 0.001）。这一发现在RCT的荟萃分析中得到进一步证实（RR：1.87，95% CI：1.42 - 2.47，p < 0.001）。与H组相比，P + H组Ⅲ/Ⅳ级腹泻的发生率更高（RR：10.54，95% CI：5.96 - 18.63，p < 0.001），但其他AE的发生率相似。tpCR（P + H vs. H，RCT）的证据质量为高，tpCR（P + H vs. H）的证据质量为中等，而tpCR（P + H vs. Per + H）的证据质量为低。
吡咯替尼联合曲妥珠单抗可能为HER2阳性乳腺癌提供一种有效的新辅助治疗选择，其疗效优于曲妥珠单抗单药治疗。然而，与Per + H相比，吡咯替尼联合曲妥珠单抗并未显示出更好的疗效。吡咯替尼联合曲妥珠单抗比曲妥珠单抗单药治疗导致更多腹泻。此外，与Per + H联合方案相比，P + H的性价比更低。
