HR+/HER2-转移性乳腺癌多线治疗后的新选择——戈沙妥珠单抗:TROPiCS-02研究结果解读

Sacituzumab Govitecan Is a New Option after Multiple Lines of Therapy for HR+/HER2-Metastatic Breast Cancer:an Interpretation of TROPiCS-02 Study

内分泌治疗耐药且经多线治疗的HR+/HER2-转移性乳腺癌面临的全身治疗药物选择非常有限。TROPiCS-02研究旨在探讨戈沙妥珠单抗对比医生选择的化疗用于内分泌治疗耐药的HR+/HER2-转移性乳腺癌患者的生存获益。2019年5月至2021年4月期间,TROPiCS-02研究共入组了北美和欧洲91个肿瘤中心的543例HR+/HER2-转移性乳腺癌患者。入组患者按1∶1随机接受戈沙妥珠单抗治疗或医生选择的化疗(艾瑞布林、长春瑞滨、卡培他滨或者吉西他滨)。患者入组标准:晚期转移性HR+/HER2-乳腺癌;入组前至少接受过内分泌治疗、紫杉类化疗和一种CDK4/6抑制剂,晚期转移性病例至少接受2~4线化疗。主要研究终点是无进展生存期,次要研究终点包括总生存期、客观缓解率、患者报告结局和安全性等。截至2022年7月,中位随访12.5个月,相比较医生选择的化疗组:戈沙妥珠单抗治疗组无进展生存期显著获益(5.5个月vs 4.0个月),进展或死亡风险减少34%(HR=0.66,95%CI:0.53~0.83,P=0.0003);显著的总生存期获益(14.4个月vs 11.2个月,HR=0.79,95%CI:0.65~0.96,P=0.020);显著的客观缓解率获益(21%vs14%,OR=1.63,95%CI:1.03~2.56,P=0.035);显著延长全球健康状况和生活质量恶化时间(4.3个月vs 3.0个月,HR=0.75,95%CI:0.61~0.92,P=0.0059)。药物毒副反应安全评估结果与之前研究报道相似。总之,戈沙妥珠单抗在治疗已经接受过治疗的内分泌抵抗性HR+/HER2-转移性乳腺癌患者中,显示出显著的无进展生存期和总生存期获益、更高的客观缓解率以及更好的健康状况和生活质量保持,药物毒副反应安全可管理。

The TROPiCS-02 study aims to investigate the survival benefits of sacituzumab govitecan compared to chemotherapy in treating endocrine therapy-resistant HR+/HER2-metastatic breast cancer,a condition with limited systemic treatment options.Conducted from May 2019 to April 2021,the study enrolled 543 patients from 91 oncology centers across North America and Europe.Participants were randomized 1∶1 into sacituzumab govitecan monotherapy(271 patients)or treatment-of-physician’s-choice chemotherapy groups(272 patients receiving eribulin,vinorelbine,capecitabine,or gemcitabine).Eligible patients had HR+/HER2-metastatic breast cancer and had undergone endocrine therapy,taxane chemotherapy,and a CDK4/6 inhibitor,with 2~4 lines of chemotherapy for advanced metastatic cases.The primary endpoint was progression-free survival(PFS),and the secondary endpoints included overall survival(OS),objective response rate(ORR),patient-reported outcomes(PRO),and safety.As of July 2022,with a median follow-up of 12.5 months,the sacituzumab govitecan group showed a significant benefit over the treatment-of-physician’s-choice chemotherapy group:longer PFS of 5.5 months compared to 4.0 months,reducing the risk of progression or death by 34%(HR=0.66,95%CI:0.53~0.83,P=0.0003),significant OS benefit of 14.4 months vs 11.2 months(HR=0.79,95%CI:0.65~0.96,P=0.020),higher ORR of 21%compared to 14%(OR=1.63,95%CI:1.03~2.56,P=0.035),extended time to deterioration(TTD)of 4.3 months vs 3.0 months(HR=0.75,95%CI:0.61~0.92,P=0.0059).Drug side effects were manageable and similar to those reported in previous studies.Sacituzumab govitecan demonstrated significant benefits in PFS,OS,higher ORR,and better maintenance of general health status and quality of life compared to treatment-of-physician’s-choice chemotherapy in patients with previously treated endocrine-resistant HR+/HER2-metastatic breast cancer.