SG（戈沙妥珠单抗）是新一代靶向Trop-2的 ADC药物，2022年6月7日获NMPA批准用于既往至少接受过2种系统治疗（其中至少1种治疗针对转移性疾病）的不可切除的局部晚期或转移性三阴性乳腺癌（TNBC）成人患者。 TROPiCS-02是一项全球性、多中心、开放标签的临床III期试验，共纳入543位HR+/HER2-转移性乳腺癌患者，按照1:1随机分配至SG组或医生选择的治疗方案（TPC，卡培他滨、艾立布林、吉西他滨或长春瑞滨）组。TROPiCS-02研究旨在探索SG在接受过内分泌治疗、CDK4/6抑制剂以及经历过2-4线化疗的HR+/HER2-晚期乳腺癌患者中的疗效与安全性[1]。研究结果显示，在意向治疗人群（ITT）中，主要研究终点盲态独立评审委员会(BICR)评估的无进展生存期（PFS），SG组为5.5个月，TPC组为4.0个月，具有统计学差异（HR=0.66，95CI% 0.53-0.83，p=0.0003），SG相比TPC组降低患者34%的疾病进展和死亡风险。本次ESMO大会报道了总生存期（OS）第二次期中分析的结果，SG组和TPC组的OS分别为14.4个月和11.2个月，具有统计学差异（HR=0.79，95CI% 0.65-0.96，p=0.020），降低患者21%的死亡风险。两组12个月的OS率分别为61%和47%[2]。 针对TROPICS-02研究，除OS第二次期中分析的结果外，此次ESMO还进一步报道了基于 HER2 IHC状态亚组分析以及生存质量（QoL）分析的结果。
-
会议编号：214MO -
研究题目：Sacituzumab govitecan efficacy in HR+/HER2- metastatic breast cancer by HER2 immunohistochemistry status in the phase 3 TROPiCS-02 study -
公布时间：9月10日 20:45-22:15（北京时间）
研究背景
研究方法
研究结果
研究结论
专家点评
-
会议编号：1553O -
研究题目：Health-related quality of life (HRQoL) in the phase 3 TROPICS-02 trial of sacituzumab govitecan (SG) vs chemotherapy in HR+/HER2- metastatic breast cancer (mBC) -
发布时间：9月11日 14:30-16:00（北京时间）
研究背景
HR+/HER2- 转移性乳腺癌患者5年生存率不足25%[13-14]。对于这一患者群体，不仅需要改进治疗方案以期提高预后生存，还需要兼顾维持生活质量[14-15]。
TROPiCS-02研究显示出SG在HR+/HER2- 转移性乳腺癌患者群体中令人鼓舞的治疗效果，能显著延长中位PFS和中位OS，且不良反应可控[1]。同时相比于TPC组，SG组显著延迟了欧洲癌症治疗研究组织（EORTC）生命质量测定量表 QLQ-C30评估的总体健康状态/QoL和疲劳至恶化时间（TTD）[2]。这项研究进一步评估了SG vs TPC对HRQOL的影响[16]。
研究方法
研究结果
具有临床意义的生活质量恶化患者比例的评估结果显示，随着时间的推移，TPC组比SG组比例更高，意味着SG在为患者提供更好疗效的同时能够维持患者的生活质量，显示出其低毒高效的特点。
研究结论
-
在先前接受治疗的内分泌耐药的HR+/HER2- 转移性乳腺癌的患者中，单药化疗临床获益有限，明显不能满足维持或改善生活质量的需求；
-
在TROPiCS-02研究中，与TPC相比，SG显示出整体的HRQoL获益，在身体功能和呼吸困难方面有所改善；
-
虽然SG组与TPC组相比腹泻加重，但与TPC组相比，SG组的其他症状和功能评分均得到改善或维持。
在TROPICS-02研究中，SG显示出在难治的HR+/HER2-转移性乳腺癌患者HRQoL的获益，加上具有统计学意义和临床意义的OS获益，这些数据支持将SG作为HR+/HER2- 转移性乳腺癌患者的重要治疗选择。
专家点评
解读专家
马力 教授
河北医科大学第四医院医院 乳腺中心
参考资料：
[1] Rugo HS, Bardia A, Marmé F, et al. Primary results from TROPiCS-02: A randomized phase 3 study of sacituzumab govitecan (SG) versus treatment of physician’s choice (TPC) in patients (Pts) with hormone receptor–positive/HER2-negative (HR+/HER2-) advanced breast cancer. presented at 2022 ASCO. LBA1001.
[2] Rugo HS, Bardia A, Marmé F, et al. Overall survival (OS) results from the phase III TROPiCS-02 study of sacituzumab govitecan (SG) vs treatment of physician's choice (TPC) in patients (pts) with HR+/HER2- metastatic breast cancer (mBC). presented at 2022 ESMO. LBA76.
[3]Schettini F, Chic N, BRASó-Maristany F, et al . Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer. NPJ Breast Cancer. 2021 Jan 4;7(1):1.
[4]P. Schmid, J. Cortés, F. Marmé, et al. Sacituzumab govitecan (SG) efficacy in hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2–) metastatic breast cancer (MBC) by HER2 immunohistochemistry (IHC) status in the phase III TROPiCS-02 study. presented at 2022 ESMO.214MO.
[5]Tarantino P, Gandini S, Nicolò E, et al. Evolution of low HER2 expression between early and advanced-stage breast cancer[J]. European Journal of Cancer, 2022, 163: 35-43.
[6]Miglietta F, Griguolo G, Bottosso M, et al. Evolution of HER2-low expression from primary to recurrent breast cancer[J]. NPJ Breast Cancer, 2021, 7(1): 1-8.
[7]Bergeron A,Bertaut A, Beltjens F,et al.A Clinicopathological Study of HER2 Status Changes between Primary Breast Cancer and Subsequent Metastasis in the New Context of HER2-Low Therapy: Are there Clinical or Pathological Characteristics that May Predict Evolution of HER2 Status? Presented at USCAP 2022.Poster Board Number:21.
[8]Fernandez A I, Liu M, Bellizzi A, et al. Examination of low ERBB2 protein expression in breast cancer tissue[J]. JAMA oncology, 2022, 8(4): 1-4.
[9]Tarantino P, Jin Q, Tayob N, et al. Prognostic and biologic significance of ERBB2-low expression in early-stage breast cancer[J]. JAMA oncology, 2022, 8(8): 1177-1183.
[10]O'Shaughnessy J, Brufsky A, Rugo H S, et al. Analysis of patients (pts) without an initial triple-negative breast cancer (TNBC) diagnosis (Dx) in the phase III ASCENT study of sacituzumab govitecan (SG) in brain metastases-negative (BMNeg) metastatic TNBC (mTNBC).presented at 2021 ESMO. e-Poster 258P.
[11]Hurvitz S A, Bardia A, Punie K, et al. Sacituzumab govitecan (SG) efficacy in patients with metastatic triple-negative breast cancer (mTNBC) by HER2 immunohistochemistry (IHC) status: Findings from the Phase 3 ASCENT study.presented at 2022 ESMO BC. 168P.
[12]Zeng P, Chen M B, Zhou L N, et al. Impact of TROP2 expression on prognosis in solid tumors: a systematic review and meta-analysis[J]. Scientific reports, 2016, 6(1): 1-7.
[13]Gonzalez-Angulo AM. et al. In: Yu D. Hung M-C. eds. Breast Cancer Chemosensitivity. New York. NY: Springer New York: 2007:1-22.
[14]Rugo H S, Bardia A, Tolaney S M, et al. TROPiCS-02: A Phase III study investigating sacituzumab govitecan in the treatment of HR+/HER2-metastatic breast cancer[J]. Future Oncology, 2020, 16(12): 705-715.
[15]Ba?aran G A, Twelves C, DiéRAS V, et al. Ongoing unmet needs in treating estrogen receptor-positive/HER2-negative metastatic breast cancer[J]. Cancer treatment reviews, 2018, 63: 144-155.
[16]H.S. Rugo, P. Schmid, S.M. Tolane,et al. Health-related quality of life (HRQoL) in the phase III TROPiCS-02 trial of sacituzumab govitecan (SG) vs chemotherapy in HR+/HER2- metastatic breast cancer (MBC).presented at 2022 ESMO. 1553O.
[17]国家药品监督管理局药品审评中心.《以临床价值为导向抗肿瘤药物临床研发的指导原则》. 2021.
[18]国家药品监督管理局药品审评中心.《患者报告结局PROs在药物临床研发中应用的指导原则试行》. 2022.
[19]Rothenberg ML. Topoisomerase I inhibitors: review and update. Ann Oncol. 1997 Sep;8(9):837-55.
[20]Spring L M, Nakajima E, Hutchinson J, et al. Sacituzumab Govitecan for Metastatic Triple-Negative Breast Cancer: Clinical Overview and Management of Potential Toxicities[J]. The Oncologist, 2021, 26(10): 827-834.
