ABSTRACT
BACKGROUND: Trastuzumab deruxtecan (T-DXd) has shown promising results in patients with breast cancer brain metastases (BCBMs). We conducted a systematic review and meta-analysis to evaluate the effectiveness and safety of T-DXd in the human epidermal growth factor receptor 2 (HER2)-positive BCBM population. PATIENTS AND METHODS: We searched PubMed, Embase, and Cochrane Library databases as well as American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), and San Antonio Breast Cancer Symposium (SABCS) websites for clinical trials (CTs) and observational studies evaluating T-DXd in patients with HER2-positive BCBM. Heterogeneity was assessed with I2 statistics. Random effects models were used for all statistical analyses, which were carried out using R software (version 4.2.2). RESULTS: Ten studies were included, six CTs (n = 189) and four observational studies (n = 130), with a total of 319 patients. The median progression-free survival was 15 months [95% confidence interval (CI) 13.9-16.1 months]. The objective response rate (ORR) was 61% (95% CI 52% to 70%), and the intracranial (IC)-ORR was 61% (95% CI 54% to 69%). No significant differences in ORR and IC-ORR were observed between CTs and observational studies (P = 0.31 and 0.58, respectively). The clinical benefit rate (CBR) was 80% (95% CI 52% to 94%), and the IC-CBR was 70% (95% CI 54% to 82%). The ORR was 68% (95% CI 57% to 77%) in the subgroup of patients with stable BMs and 60% (95% CI 48%-72%) in patients with active BM, with no significant difference between groups (P = 0.35). CONCLUSIONS: Our systematic review and meta-analysis supports the IC activity of T-DXd in patients with stable BM and active BM. TRIAL REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) under the protocol number CRD42023422589.
Subject(s)
Brain Neoplasms , Breast Neoplasms , Camptothecin/analogs & derivatives , Immunoconjugates , Receptor, ErbB-2 , Humans , Female , Breast Neoplasms/drug therapy , Trastuzumab/pharmacology , Trastuzumab/therapeutic use , Brain Neoplasms/drug therapyABSTRACT
The long-lived xenon isomers 129mXe and 131mXe are of interest for the GAMMA-MRI project, which aims at developing a novel imaging modality based on magnetic resonance of polarized unstable tracers. Here, we present the steps leading to and following the production of these two isomers via neutron irradiation of highly-enriched 128Xe and 130Xe gas samples at two high-flux reactors, the High-Flux Reactor (Réacteur à haut flux, RHF) at the Institut Laue-Langevin (ILL) and the MARIA reactor at the National Centre for Nuclear Research (NCBJ). We describe the experimental setups and procedures used to prepare the stable xenon samples, to open the irradiated samples, and to transfer xenon isomers into reusable transport vials. The activity of 129mXe and 131mXe was measured to be in the range of tens of MBq per sample of 0.8(1)mg, and was proportional to thermal neutron flux density. A small activity of unstable contaminants was also visible in the samples, but their level is not limiting for the GAMMA-MRI project's objectives. In addition, the minimum thermal neutron flux density required to produce 129mXe and 131mXe sufficient for the project could be also determined.
