吡咯替尼联合或不联合曲妥珠单抗治疗经治 HER2 阳性转移性结直肠癌的疗效：一项前瞻性观察研究的结果。

Efficacy of Pyrotinib With/Without Trastuzumab in Treatment-Refractory, HER2-Positive Metastatic Colorectal Cancer: Result From a Prospective Observational Study.

机构信息

Department of Oncology, Zhongshan Hospital, Fudan University, Shanghai, China; Department of Oncology, Central Hospital of Xuhui District, Shanghai, China.

Department of Cancer Prevention and Screening, Zhongshan Hospital, Fudan University, Shanghai, China; Department of Biostatistics, Zhongshan Hospital, Fudan University, Shanghai, China; Department of Evidence-based Medicine, Fudan University, Shanghai, China.

出版信息

Clin Colorectal Cancer. 2024 Mar;23(1):58-66. doi: 10.1016/j.clcc.2023.10.008. Epub 2023 Nov 19.

DOI:10.1016/j.clcc.2023.10.008

PMID:38177002

Abstract

BACKGROUND

Human epidermal growth factor receptor 2 (HER2) is a promising therapeutic target in metastatic colorectal cancer (mCRC). This study was to evaluate the efficacy and safety of pyrotinib alone or pyrotinib with trastuzumab in patients with HER2-positive mCRC.

PATIENTS AND METHODS

In this prospective observational study, patients with HER2 positive, Ras Sarcoma Viral Oncogene Homolog (RAS) wild type mCRC who received at least one standard treatment of palliative chemotherapy were enrolled. Patients were treated with oral pyrotinib alone or pyrotinib with trastuzumab. The primary endpoint was progression free survival (PFS), and the secondary endpoints were overall survival (OS), confirmed objective response rate (ORR), and safety. This trial is registered with chitcr.org, number ChiCTR2100046381.

RESULTS

From February 15, 2021, to January 10, 2023, 32 patients were enrolled in this study. Twenty (62.5%) patients were treated with pyrotinib, while 12 (37.5%) received pyrotinib and trastuzumab. As of June 24, 2023, with a median follow-up of 11.0 months, the median PFS was 5.7 months (95%CI 4.5-10.2), while OS was not evaluable (NE), ORR and disease control rate (DCR were 34.4% and 87.5%. Patients' PFS in the pyrotinib plus trastuzumab subgroup and pyrotinib monotherapy group were 8.6 and 5.5 months, OS was not evaluable (NE) and 10.9 months, ORR was 50.0% and 25.0%, respectively. Most treatment-related adverse events (TRAEs) were grade 1-2, diarrhea was the most frequent TRAE (81.3%, 26/32). Grade 3 TRAEs occurred in 11 patients: 9 for diarrhea, 1 for nausea, and 1 for oral mucositis.

CONCLUSION

Pyrotinib with or without trastuzumab showed promising anti-tumor activity and acceptable toxicities in treatment-refractory, HER2-positive mCRC.

摘要

背景

人表皮生长因子受体 2（HER2）是转移性结直肠癌（mCRC）有前途的治疗靶点。本研究旨在评估吡咯替尼单药或联合曲妥珠单抗治疗 HER2 阳性 mCRC 的疗效和安全性。

患者和方法

在这项前瞻性观察性研究中，招募了接受至少一种姑息性化疗标准治疗后 HER2 阳性、Ras 肉瘤病毒致癌基因同源物（RAS）野生型 mCRC 的患者。患者接受口服吡咯替尼单药或吡咯替尼联合曲妥珠单抗治疗。主要终点是无进展生存期（PFS），次要终点是总生存期（OS）、确认的客观缓解率（ORR）和安全性。本试验在中国临床试验注册中心注册，注册号 ChiCTR2100046381。

结果

从 2021 年 2 月 15 日至 2023 年 1 月 10 日，共有 32 名患者入组本研究。20 名（62.5%）患者接受吡咯替尼治疗，12 名（37.5%）接受吡咯替尼联合曲妥珠单抗治疗。截至 2023 年 6 月 24 日，中位随访时间为 11.0 个月，中位 PFS 为 5.7 个月（95%CI 4.5-10.2），OS 不可评估（NE），ORR 和疾病控制率（DCR 分别为 34.4%和 87.5%。吡咯替尼联合曲妥珠单抗亚组和吡咯替尼单药组患者的 PFS 分别为 8.6 和 5.5 个月，OS 不可评估（NE）和 10.9 个月，ORR 分别为 50.0%和 25.0%。大多数治疗相关不良事件（TRAEs）为 1-2 级，腹泻是最常见的 TRAE（81.3%，26/32）。3 级 TRAE 发生在 11 名患者中：9 名腹泻，1 名恶心，1 名口腔粘膜炎。