吡咯替尼联合方案治疗人表皮生长因子受体 2 阳性转移性乳腺癌的疗效和安全性：一项多中心真实世界研究。

Efficacy and safety of pyrotinib-containing regimen in the patients with HER2-positive metastatic breast cancer: A multicenter real-world study.

机构信息

Department of Breast Medical Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong Province, China.

School of Medicine, Nankai University, Tianjin, China.

出版信息

Cancer Med. 2023 Feb;12(3):2333-2344. doi: 10.1002/cam4.5056. Epub 2022 Jul 27.

BACKGROUND

Pyrotinib, a novel irreversible epidermal growth factor receptor 2 (EGFR)/HER2 dual tyrosine kinase inhibitor, has shown promising antitumor efficacy with tolerable toxicity in HER2-positive metastatic breast cancer (MBC) in several clinical trials. However, the clinical trials do not usually well reflect the patients in real clinical settings. Despite several small-sample studies in real world, the data on pyrotinib as first-line and third-or-later-line treatment and the efficacy comparison of pyrotinib combined with different regimens are still lacking. Therefore, this study aimed to investigate the efficacy and safety of pyrotinib for the HER2-positive MBC in real world to replenish more comprehensive data.

METHODS

A total of 172 HER2-positive MBC patients treated with pyrotinib-based therapy were recruited from multiple centers in nonclinical trial settings from September 2017 to June 2020.

RESULTS

The median progression-free survival (mPFS) of 172 patients was 8.83 months. The patients, receiving first-line pyrotinib treatment, had the longest mPFS (20.93 months) compared with those receiving second-line (8.67 months, p = 0.0339) and third-or-later-line (7.13 months, p = 0.0075) treatments, respectively. Prior treatment with lapatinib (p = 0.012) and site of metastasis (visceral vs. nonvisceral) (p = 0.033) were the independent prognostic factors for PFS. The prior treatment with lapatinib compared with lapatinib-native treatment (5.96 vs. 10.97 months, p = 0.0036) and those with visceral metastasis compared with nonvisceral metastasis (8.40 vs. 23.70 months, p = 0.0138) had worse mPFS. Among 146 patients evaluated for efficacy, 2.1%, 58.9%, and 32.9% showed complete response, partial response, and stable disease, respectively. Adverse events occurred in 92.4% of the patients with 33.3% Grade 3 and higher adverse events and diarrhea (57.0%), anemia (44.8%), and leukopenia (40.7%) as the most frequent ones.

CONCLUSIONS

Pyrotinib-containing regimen could effectively treat HER2-positive MBC with acceptable toxicity, including the patients who progressed after lapatinib treatment and with brain metastasis.

背景

吡咯替尼是一种新型不可逆表皮生长因子受体 2（EGFR）/人表皮生长因子受体 2（HER2）双重酪氨酸激酶抑制剂，在几项临床试验中显示出对 HER2 阳性转移性乳腺癌（MBC）有良好的抗肿瘤疗效和可耐受的毒性。然而，临床试验通常并不能很好地反映真实临床环境中的患者情况。尽管在真实世界中进行了几项小样本研究，但关于吡咯替尼作为一线和三线或以后线治疗的疗效以及与不同方案联合使用的疗效比较的数据仍然缺乏。因此，本研究旨在调查吡咯替尼在真实世界中治疗 HER2 阳性 MBC 的疗效和安全性，以补充更全面的数据。

方法

本研究共纳入了 172 例来自多个中心的非临床试验环境中接受吡咯替尼治疗的 HER2 阳性 MBC 患者，入组时间为 2017 年 9 月至 2020 年 6 月。

结果

172 例患者的中位无进展生存期（mPFS）为 8.83 个月。与二线（8.67 个月，p=0.0339）和三线或以后线（7.13 个月，p=0.0075）治疗相比，接受一线吡咯替尼治疗的患者 mPFS 最长（20.93 个月）。既往接受拉帕替尼治疗（p=0.012）和转移部位（内脏 vs. 非内脏）（p=0.033）是 PFS 的独立预后因素。与拉帕替尼初治相比，既往接受拉帕替尼治疗的患者 mPFS 更差（5.96 个月 vs. 10.97 个月，p=0.0036），与无内脏转移相比，有内脏转移的患者 mPFS 更差（8.40 个月 vs. 23.70 个月，p=0.0138）。在 146 例可评估疗效的患者中，分别有 2.1%、58.9%和 32.9%的患者达到完全缓解、部分缓解和疾病稳定。92.4%的患者发生不良反应，33.3%的患者为 3 级及以上不良反应，最常见的不良反应为腹泻（57.0%）、贫血（44.8%）和白细胞减少（40.7%）。