Trastuzumab deruxtecan for the treatment of patients with HER2-positive breast cancer with brain and/or leptomeningeal metastases: an updated overall survival analysis using data from a multicenter retrospective study (ROSET-BM).

We provide updated results (median follow-up duration: 20.4 months) of a retrospective study on the effectiveness of trastuzumab deruxtecan (T-DXd) in patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer with brain metastases (BM) and/or leptomeningeal disease (ROSET-BM). Median progression-free survival (PFS) was 14.6 months. Median overall survival (OS) was not reached (NR); 24-month OS rate was 56.0%. Subgroup analysis showed that median PFS was 13.2 months in patients with analytical active BM, 17.5 months in patients with leptomeningeal carcinomatosis (LMC), and NR in patients with analytical stable BM (24-month PFS rates in patients with analytical active BM, LMC, and analytical stable BM were 32.7%, 25.1%, and 60.8%, respectively). Median OS was 27.0 months in patients with analytical active BM and NR in patients with LMC or analytical stable BM (24-month OS rates in patients with analytical active BM, LMC, and analytical stable BM were 52.0%, 61.6%, and 71.6%, respectively). The most common adverse event leading to discontinuation of T-DXd was interstitial lung disease (ILD; 23.1%); median ILD onset time among patients who discontinued T-DXd treatment due to ILD was 5.3 months. T-DXd has promising effectiveness in heavily pre-treated HER2+ metastatic breast cancer patients with BM and LMC. The incidence and median onset time of ILD were similar to those of Japanese subgroups in previous studies.

Multicentre, randomised, double-blind, placebo-controlled phase II study of prophylactic olanzapine for patients with metastatic breast cancer receiving T-DXd treatment: protocol for the ERICA study (WJOG14320B).

INTRODUCTION: The antibody-drug conjugate trastuzumab deruxtecan (T-DXd) has led to a change in the clinical management of breast cancer. Nausea and vomiting are the most common adverse events of T-DXd, which cannot be completely alleviated by standard prophylactic regimens. Olanzapine is particularly effective in preventing delayed nausea caused by chemotherapy. In this study, we will evaluate the efficacy of olanzapine in managing persistent nausea and vomiting during T-DXd treatment. METHODS AND ANALYSIS: The ERICA study is a multicentre, placebo-controlled, double-blind, randomised phase II study with the aim to evaluate the antiemetic effects of the prophylactic olanzapine (5 mg orally, on days 1-6) or placebo combined with a 1,5-hydroxytryptamine-3 (5-HT3)-receptor antagonist and dexamethasone in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer undergoing T-DXd treatment. For a period of 22 days from the day of T-DXd treatment, patients will document their experience in an electronic symptom diary daily during observational periods. The primary endpoint is the complete response rate, defined as no vomiting and no rescue medications during the 'delayed phase' of 24-120 hours post-T-DXd administration. In addition, we define 120-504 hour as the 'persistent phase' and 0-504 hours as the 'overall phase' for secondary endpoint analysis. We have estimated that a total sample size of at least 156 patients is needed to allow a power of 80% at a one-sided significance level of 20% in this study. The target sample size is set to 166 to account for possible case exclusions. ETHICS AND DISSEMINATION: The study protocol is approved by the West Japan Oncology Group protocol review committee and the SHOWA University Clinical Research Review Board. The study results will be presented at international conferences and published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: jRCTs031210410.