Durable Effect of Pyrotinib and Metronomic Vinorelbine in HER2-Positive Breast Cancer With Leptomeningeal Disease: A Case Report and Literature Review.

Yajing Chi,Binbin Cong,Baoxuan Zhang,Lihua Song,Mao Shang,Rongjie Tao,Huihui Li,Sha Yin,Heyi Gong,Liang Xu

doi:10.3389/fonc.2022.811919

Abstract

Leptomeningeal metastases (LM) are rare and catastrophic for metastatic breast cancer (MBC). The prognosis of HER2-positive breast cancer (BC) with LM is extremely poor. There is no high-quality evidence of treatment regimens in HER2-positive BC with LM yet. Here, we present a case of LM in a 50-year-old woman with HER2-positive BC. Immunohistochemistry revealed invasive ductal carcinoma, estrogen receptor negative, progesterone receptor negative, HER2 3+, P53 positive 80%, and Ki-67 positive 35%. Reported for the first time, the patient was given pyrotinib-targeted therapy (400 mg, oral, every day), metronomic vinorelbine (40 mg, oral, three times a week), and intrathecal methotrexate (10 mg, infrequent and irregular use due to poor compliance) synchronously. The patient received and benefited from the treatment regimen for 16 months. And the quality of life, as self-reported, improved significantly. We also comprehensively summarized all the case reports, observational studies, and clinical trials related to HER2-positive BC with LM in the PubMed database and ClinicalTrials.gov. Intrathecal chemotherapy (methotrexate, cytarabine, thiotepa), intrathecal trastuzumab, whole-brain radiotherapy, and systemic therapy are commonly used treatment options according to a review of the literature and research. Pembrolizumab and trastuzumab deruxtecan (DS-8201) as novel drugs are promising in LM. Furthermore, trastuzumab emtansine (T-DM1) and tyrosine kinase inhibitors (TKIs) such as tucatinib and neratinib have exhibited good efficacy in HER2-positive BC with central nervous system (CNS) metastases and deserve further exploration. In our report, combining pyrotinib-targeted therapy with metronomic chemotherapy is a potential regimen, which has presented satisfactory therapeutic efficacy and also warrants additional investigation in HER2-positive BC with LM.

Highlights

Breast cancer (BC) is the most widespread cancer and the primary tumor-related reason for death in women around the globe [1]
19 of 28 observational studies, 9 of 10 ongoing clinical trials, and 4 of 18 completed clinical trials in our review related to leptomeningeal metastases (LM) in BC included Human epidermal growth factor receptor 2 (HER2)-positive BC patients (Figure 3)
Compared with the combination of placebo and capecitabine, pyrotinib plus capecitabine was demonstrated to significantly prolong the Median progression-free survival (mPFS) (11.1 vs. 4.1 months, p

Summary

Introduction

Breast cancer (BC) is the most widespread cancer and the primary tumor-related reason for death in women around the globe [1]. Accounting for 1% to 5% in BC, leptomeningeal metastases (LM) is closely linked to high mortality [2]. BC patients with LM have worse prognoses, compared to patients with metastases to other sites [3,4,5]. The survival of untreated BC patients with LM is only about 1 month, and even after treatment, the average survival time seldom reach 8 months [6]. Treatment choices mainly include radiotherapy, intrathecal chemotherapy, systemic treatment, and symptomatic care. But combining or choosing among them remains difficult due to the limitations and of these therapies and their varying degree of tolerability by patients. Intrathecal chemotherapy often exhibits potentially severe neurotoxicity, usually late in the course of treatment. Systemic chemotherapy or targeted therapy has a limited ability to penetrate the blood-brain barrier

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