Abstract PS5-02-12: Intracranial Activity and Systemic Efficacy of Trastuzumab Deruxtecan in Breast Cancer Patients with Brain Metastases

Abstract Background: Trastuzumab deruxtecan (T-DXd), a novel antibody-drug conjugate (ADC), has shown promising intracranial efficacy in breast cancer (BC) patients with brain metastases (BM). This meta-analysis evaluates the intracranial activity and systemic efficacy of T-DXd in patients with metastatic BC and BM. Methods: A systematic search was conducted from inception until May 6, 2025, across PubMed, Cochrane Library, and oncology conference abstracts (ASCO, ESMO, SABCS, and EANO). Eligible studies included clinical trials and cohort studies reporting outcomes for BC patients with BM receiving T-DXd. Random-effects meta-analysis models with Freeman-Tukey transformations were used for pooling proportions (intracranial clinical benefit rate [IC-CBR], intracranial objective response rate [IC-ORR], and 12-month systemic overall survival [OS]). Systemic progression-free survival (PFS) was pooled using a random-effects inverse-variance model. For PFS, means and standard deviations (SDs) were extracted when available or estimated from medians and IQRs using the Wan et al. (2014) method: mean = (Q1 + median + Q3)/3 and SD = (Q3 − Q1)/1.35, adjusted for sample size. Heterogeneity was assessed using the I2 statistic, with values ≤25% considered low, 26-75% moderate, and >75% high. Registration: osf.io/swghm. Results: Of the 489 screened records, 14 studies were included; 1 was a randomized controlled trial, 6 were prospective single-arm trials, and 7 were retrospective cohort studies, including real-world data from early access programs. Median patient age was 56.3 years; 97.3% had HER2-positive BC, and 2.7% HER2-low. Prior cranial radiotherapy was administered in 61%, with concurrent radiotherapy at T-DXd initiation in 1.4%. Median follow-up duration was 12.9 months (IQR: 11-15). T-DXd was administered uniformly at 5.4 mg/kg IV every three weeks, with protocol-specified dose reductions allowed. Pooled IC-CBR was 81% (95% CI: 69-91%, p