三阴性乳腺癌术前免疫化疗新方案

　　三阴性乳腺癌的雌激素受体、孕激素受体、人类表皮生长因子受体HER2均为阴性，对内分泌治疗和HER2靶向治疗效果较差，对于高风险早期患者，术前新辅助化疗仍然是主要选择，不仅可以缩小较大的肿瘤，提高手术的可行性、成功率和保乳率，还可指导术后治疗。不过，早期三阴性乳腺癌仅仅依靠术前新辅助化疗的病理完全缓解率仅30%～50%。KEYNOTE-522、IMpassion031研究已经证实免疫检查点抑制剂帕博利珠单抗、阿替利珠单抗联合术前新辅助化疗可将早期三阴性乳腺癌的病理完全缓解率分别由51.2%、41%提高至64.8%、58%。中国原研的免疫检查点抑制剂卡瑞利珠单抗已被证实联合化疗对晚期三阴性乳腺癌有效，对早期三阴性乳腺癌的疗效尚不明确。

　　2023年10月20日，英国《自然》旗下《自然通讯》在线发表河南省肿瘤医院（郑州大学附属肿瘤医院）王承正、刘真真＠、陈秀春、乔江华、卢振铎、李连方、孙献甫、张崇建、夏庆欣、张贺、闫敏等学者的HR-TNBC-HN100研究报告，首次探讨了早期三阴性乳腺癌术前卡瑞利珠单抗＋白蛋白结合型紫杉醇＋表柔比星新辅助化疗的有效性和安全性。

HR-TNBC-HN100 (NCT04213898): SHR-1210 Combined With Albumin-bound Paclitaxel and Epirubicin Neoadjuvant for Triple Negative Breast Cancer

　　该单中心单组二期临床研究于2020年1月～2021年10月入组年龄≥18岁、组织学证实早期三阴性乳腺癌尚未治疗的女性患者39例，术前每3周第1天给予卡瑞利珠单抗200 mg、表柔比星75 mg / m²，第1、8和15天给予白蛋白结合型紫杉醇125 mg / m²，连续6个周期。主要终点为病理完全缓解；次要终点包括安全性、客观缓解率、长期生存结局（无事件生存、无病生存、远处无病生存）。

　　结果，25例患者获得病理完全缓解，病理完全缓解率达64.1%（95%置信区间：47.2～78.8）。客观缓解率达89.7%（95%置信区间：74.8～96.7），其中部分缓解患者35例。30例患者（76.9%）发生3或4级治疗相关不良事件。

　　因此，该初步研究结果表明，术前卡瑞利珠单抗＋白蛋白结合型紫杉醇＋表柔比星新辅助化疗对早期三阴性乳腺癌女性患者疗效令人鼓舞、安全性可控，长期生存结局值得期待，并有必要进一步开展多中心大样本随机对照研究进行验证。

相关链接

• 新英格兰：Ｋ药治疗早期三阴性乳腺癌
• 柳叶刀正刊首发三阴性乳腺癌治疗方案
  

Nat Commun. 2023 Oct 20;14:6654. IF: 16.6

Neoadjuvant camrelizumab plus nab-paclitaxel and epirubicin in early triple-negative breast cancer: a single-arm phase II trial.

Wang C, Liu Z, Chen X, Qiao J, Lu Z, Li L, Sun X, Zhang C, Yue X, Xia Q, Zhang H, Yan M.

The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.

Immunotherapy combined with chemotherapy has been demonstrated to be effective in early triple-negative breast cancer (TNBC). In this single-arm, phase II study with Simon's two-stage design, we investigated the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy in patients with early TNBC (NCT04213898). Eligible female patients aged 18 years or older with histologically confirmed treatment-naive early TNBC were treated with camrelizumab (200 mg, on day 1), nab-paclitaxel (125 mg/m2, on days 1, 8, and 15), and epirubicin (75 mg/m2, on day 1) every three weeks for six cycles. The primary end point was the pathological complete response; secondary endpoints included safety, objective response rate, and long-term survival outcomes of event-free survival, disease-free survival, and distant disease-free survival. A total of 39 patients were enrolled between January 2020 and October 2021. Twenty-five patients achieved a pathological complete response (64.1%, 95%CI: 47.2, 78.8). The objective response rate was 89.7% (95%CI: 74.8, 96.7), including 35 patients with partial responses. Treatment-related adverse events of grade 3 or 4 occurred in 30 (76.9%) patients. In conclusion, the trial meets the prespecified endpoints showing promising efficacy and manageable safety of neoadjuvant camrelizumab plus nab-paclitaxel and epirubicin chemotherapy in female patients with early TNBC. Long-term survival outcomes are still pending.

PMID: 37863916

DOI: 10.1038/s41467-023-42479-w