Phase I Study and Cell-Free DNA Analysis of T-DM1 and Metronomic Temozolomide for Secondary Prevention of HER2-Positive Breast Cancer Brain Metastases

This study is a phase I trial combining ado-trastuzumab emtansine (T-DM1) with Temozolomide (TMZ) for the prevention of additional brain metastases after previous occurrence and local treatment in HER2+ breast cancer patients. Twelve patients were enrolled in this study. Data includes whole exome sequencing (WES) from patients' cerebrospinal fluid (CSF) and plasma samples. The CSF was collected from each patient at trial entry and after the initial two treatment cycles of TMZ and T-DM1 treatment. Blood was collected through a standard peripheral venipuncture at the following four time points: 1) upon trial entry, 2) after two treatment cycles, 3) the treatment cycle prior to the last follow-up, and 4) most recent follow-up. Whole exome libraries were captured by the SureSelect Human All Exon V8 Kit (Agilent, Santa Clara, CA, USA) and sequenced by NovaSeq 6000 S2 Sequencer in paired-end sequencing mode (Illumina, San Diego, CA, USA). Gene mutations in DNMT3A, ELP1, NOTCH4, KMT2B, CRLF2, and KCNJ18 were observed in patients' CSF.]]>
Inclusion Criteria18 years of age or olderEastern Cooperative Oncology Group (ECOG) performance status <2Histologically confirmed HER2-positive metastatic breast cancer and adequate organ and marrow function. Had brain metastases that had been treated with stereotactic radiosurgery (SRS), surgical resection, or whole brain radiation therapy (WBRT) within 12 weeks of study enrollment. Previous treatment with T-DM1 was allowed if patient did not have systemic progression while on it.Exclusion CriteriaKnown leptomeningeal metastatic disease Had chronic viral infections, impaired cardiac function, recent pulmonary embolism, significant peripheral neuropathy, or recent cerebral vascular accident or transient ischemic attack ]]>