吡咯替尼治疗晚期乳腺癌真实效果

　　吡咯替尼是中国原创的HER1、HER2和HER4酪氨酸激酶不可逆抑制剂。随机对照前瞻研究、真实世界回顾研究已经证实，吡咯替尼＋卡培他滨与拉帕替尼＋卡培他滨相比，可显著改善HER2阳性晚期乳腺癌患者的无进展生存和客观缓解率。不过，吡咯替尼治疗HER2阳性晚期乳腺癌的真实世界前瞻研究极少。

　　2021年7月16日，瑞士《肿瘤学前沿》在线发表江苏省肿瘤医院、江苏省肿瘤研究所、南京医科大学附属肿瘤医院、江南大学附属医院、连云港市第一人民医院、连云港市第二人民医院、镇江市第一人民医院、苏州大学附属第二医院、徐州医科大学附属医院、无锡市人民医院、南京鼓楼医院集团宿迁市人民医院、苏州大学附属第三医院、常州市第一人民医院、苏州大学附属第一医院、徐州市中心医院、南京鼓楼医院、南京大学医学院附属医院、苏州市立医院、南京医科大学附属苏州医院、盐城市第一人民医院的多中心真实世界前瞻非对照研究，对吡咯替尼治疗HER2阳性晚期乳腺癌的患者特征、治疗方案和临床结局进行了分析。

　　该多中心真实世界前瞻非对照研究于2019年2月～2020年4月从中国15家医院入组HER2阳性晚期乳腺癌患者141例，并随访至2021年2月。全部患者口服吡咯替尼，起始剂量、联合化疗药物和（或）其他HER2靶向药物和（或）放疗根据既往临床试验结果、患者整体健康状况和意愿由医师自行选择。主要终点为无进展生存。该研究于2019年2月28日获得江苏省肿瘤医院伦理委员会批准，2019年3月11日在中国临床试验注册中心注册（注册号：ChiCTR1900021819）。

　　结果，中位无进展生存：

  • 全部患者：12.0个月（95%置信区间：8.1～17.8）

  • 有肝转移：8.7个月（95%置信区间：6.3～15.4）

  • 无肝转移：12.3个月（95%置信区间：8.8～23.3，P=0.172）

  • 大于二线治疗：8.4个月（95%置信区间：5.9～15.4）

  • 一或二线治疗：15.1个月（95%置信区间：9.3～22.9，P=0.107）

  • 用过曲妥珠单抗：12.2个月（95%置信区间：7.9～18.8）

  • 未用曲妥珠单抗：11.8个月（95%置信区间：6.8～22.9，P=0.732）

  • 化疗有卡培他滨：15.1个月（95%置信区间：10.0～18.8）

  • 化疗无卡培他滨：8.4个月（95%置信区间：6.7～22.9，P=0.070）

　　此外，脑转移患者的无进展生存率：

  • 6个月：70.0%

  • 12个月：60.0%

　　70例病变可测量患者：

  • 客观缓解率：38.6%

  • 病变控制率：85.7%

　　发生率最高的不良事件为腹泻（85.0%）。

　　因此，该多中心小样本真实世界前瞻非对照研究结果表明，吡咯替尼治疗HER2阳性乳腺癌患者的效果令人鼓舞、耐受性良好，即使用过曲妥珠单抗，尤其对于吡咯替尼一或二线治疗和卡培他滨化疗患者，疗效优于曲妥珠单抗、帕妥珠单抗、恩美曲妥珠单抗等其他抗HER2新药的历史数据，故有必要进一步开展头对头研究与曲妥珠单抗、帕妥珠单抗、恩美曲妥珠单抗等其他抗HER2新药进行直接比较。

Front Oncol. 2021 Jul 16;11:699323.

Pyrotinib in the Treatment of Women With HER2-Positive Advanced Breast Cancer: A Multicenter, Prospective, Real-World Study.

Zhang L, Wu X, Zhou J, Zhu M, Yu H, Zhang Y, Zhao Y, Han Z, Guo Y, Guan X, Wang X, Xu H, Sun L, Zhang J, Zhuang M, Xie L, Yu S, Chen P, Feng J.

Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China; Affiliated Hospital of Jiangnan University, Wuxi, China; The First People's Hospital of Lianyungang, Lianyungang, China; The Second People's Hospital of Lianyungang, Lianyungang, China; Zhenjiang First People's Hospital, Zhenjiang, China; The Second Affiliated Hospital of Soochow University, Suzhou, China; The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China; Wuxi People's Hospital, Wuxi, China; Suqian People's Hospital of Nanjing Drum-Tower Hospital Group, Suqian, China; The Third Affiliated Hospital of Soochow University, The First People's Hospital of Changzhou, Changzhou, China; The First Affiliated Hospital of Soochow University, Suzhou, China; Xuzhou Central Hospital, Xuzhou, China; Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China; Suzhou Municipal Hospital, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China; Yancheng No.1 People's Hospital, Yancheng, China.

BACKGROUND: HER2-positive breast cancer was aggressive, resulting in a poorer prognosis. This multicenter study analyzed the real-world data of women treated with pyrotinib-based therapy, aiming to describe their characteristics, treatment regimens, and to investigate the clinical outcomes.

METHODS: A total of 141 patients with HER2-positive breast cancer were enrolled from February 2019 to April 2020. Last follow-up time was February 2021. All patients were treated with pyrotinib-based therapy in 21-day cycles. The primary endpoint was progression-free survival (PFS).

RESULTS: The median PFS (mPFS) for pyrotinib-based therapy was 12.0 months (95%CI 8.1-17.8) in all patients. Among the patients with liver metastases, mPFS was 8.7 months (95%CI, 6.3-15.4) compared to 12.3 months (95%CI, 8.8-23.3) for patients without liver metastases (P=0.172). In addition, patients receiving pyrotinib-based therapy as their >2 lines treatment had a numerically lower mPFS than those receiving pyrotinib-based therapy as their ≤2 lines treatment [8.4 (95%CI, 5.9-15.4) vs. 15.1 (95%CI, 9.3-22.9) months, P=0.107]. The mPFS was 12.2 months (95%CI, 7.9-18.8) in patients with previous exposure to trastuzumab and 11.8 months (95%CI, 6.8-22.9) in patients without previous exposure to trastuzumab (P=0.732). Moreover, mPFS in patients receiving regimens with and without capecitabine were 15.1 months (95%CI, 10.0-18.8) and 8.4 months (95%CI, 6.7-22.9), respectively (P=0.070). Furthermore, in patients with brain metastases, estimated 6-month PFS rate was 70.0%, and rate at 12 months was 60.0%. Seventy patients with measurable lesions were evaluable for response. The objective response rate was 38.6% and disease control rate was 85.7%. The most common adverse event was diarrhea (85.0%).

CONCLUSION: Pyrotinib-based therapy showed promising efficacy in patients with HER2-positive breast cancer and was well tolerated, especially in patients treated with pyrotinib as ≤2 lines treatment and receiving regimens with capecitabine. The results of this real-world study further confirmed the intriguing efficacy of pyrotinib.

KEYWORDS: brain metastasis; breast cancer; human epidermal growth factor receptor 2; pyrotinib; real-world

PMID: 34336688

PMCID: PMC8322968

DOI: 10.3389/fonc.2021.699323

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