A meta-analysis analyzing the efficacy of trastuzumab-deruxtecan (T-DXd) on central nervous system (CNS) disease in patients with metastatic breast cancer (mBC).

Abstract

e14012 Background: CNS metastasis from mBC portends a poor prognosis. We sought to analyze CNS activity of T-DXd through a meta-analysis. Methods: A systematic search with terms encompassing BC and T-DXd was conducted in PubMed, Embase, Scopus, and Cochrane on November 23 2023. There were no search restrictions. A total of 2318 records were identified, and duplicates were removed using Mendeley. 1189 records that remained were imported into Rayyan, and the titles were screened independently by 2 reviewers. 47/75 full texts were relevant, of which 12 [7 clinical trials and 5 retrospective study] were included for analysis. Only studies that provided stratified CNS response data for mBC were included. RevMan was used to analyze the Risk Ratio (RR) and Odds Ratio (OR) with 95% Confidence Interval (CI), derived from Random Effects (RE) model with Mantel-Haenszel (MH) method. Binary RE Pooled Proportions (PP) using DerSimonian-Laird method were determined using OpenMeta. Visual inspection of our funnel plots revealed no bias. Results: The T-DXd cohort had a total of 377 patients with a median age of 54.2 years (42.5-69). Control group (T-DM1-1, Chemotherapy-2 studies) had 86 patients with a median age of 54.5 years (54.2-54.7). All studies had previously treated patients and most of the patients received local therapy. PP with T-DXd for CNS Complete Response (CR) was 4.8% (2-7.6%). Partial Response (PR) was 50.1% (32.4-67.7%) and Stable Disease (SD) was 28.9 (20.5-37.3%). PP of Objective Response Rate (ORR) (CR+PR) was 60.9% (48.3-73.5%). Drug discontinuation rate was 18% (12.2-23.9%) and pneumonitis rate was 14.5% (9.4-19.6%). RR for Event/Progressive Disease (PD) comparing T-DXd and control group was not significant [0.96 (0.77,1.2) p=0.74, I²=0%], nor was OR for Disease Control Rate (DCR) (CR+PR+SD) [1.11 (0.63,1.96) p=0.64, I²=0%] (Table). The median Progression Free Survival (PFS) was 14.1 (8.5-18.1) months for the T-DXd and 4.3 (3-5.6) months for the control group. Conclusions: Although direct comparison between the pooled T-DXd and control group failed to reveal a difference, the pooled ORR from 10/12 studies was clinically significant at 60.9%. The median PFS for T-DXd was also longer. T-DXd could be a viable treatment option for pretreated HER2+ and low mBC with CNS metastasis. Limitation of our study is the heterogeneity between the studies, entailing the need for future clinical trials in this setting. [Table: see text]