Trastuzumab deruxtecan (T-DXd) in HER2-positive advanced breast cancer (ABC) with active CNS metastases: Real world data.

e13024 Background: T-DXd is considered one of the promising agents for the treatment of HER2+ ABC including patients (pts) with metastases (mts) to the CNS. However, data on its intracranial effectiveness in patients with active brain metastases (ABM) are limited (DB-012 study included 106 pts with ABM). There is the retrospective analysis of the efficacy and safety of T-DXd in 70 pts with HER2+ ABM in real practice of several Moscow clinics. Methods: Since Jul 2024 70 HER2+ ABC pts with active CNS mts (one - with leptomeningeal metastases) has started treatment with T-DXd at a dose of 5.4 mg/kg every 3 weeks until disease progression or unacceptable toxicity. All of them has disease progression on at least one line of therapy including neo-/adjuvant setting. Metastases were considered active either without previous local treatment (eg, radiotherapy) or with CNS progression after previous local treatment. The primary endpoint is median progression-free survival (PFS); secondary endpoints include 12-month intracranial progression-free survival (icPFS), objective response rate (ORR), intracranial ORR (icORR) and clinical benefit (CB) defined per RECIST 1.1, safety and median overall survival (OS). The data cutoff is 13 JAN 2025. Results: 70 pts, all female with median age 50 y.o. (range 31-66) has started T-DXd therapy in Moscow Cancer Centers. Median lines of previous treatment in ABC was four (0-11), the most pts have received pertuzumab (n = 61, 87%), 19 of them (31%) in neoadjuvant setting. With T-DM1 were treated 58 pts (83%), with lapatinib – 23 pts (33%); all 3 anti-HER2 Rx received 17 pts (24%). At the time of initiation of therapy with T-DXd, 19 patients had brain mts only. 30 pts had untreated ABM (group 1); 40 had previously treated ABM that were progressive at start therapy with T-DXd (group 2). Currently, 64 patients (91,4%) remain on therapy; 61 patients completed at least one effect assessment, and 2 more progressed to the first assessment. Intracranial clinical benefit was observed in 51 (83%) of 61 patients evaluated. 4 (6,6%) complete intracranial responses were recorded (3 in group 1 and 1 in group 2), 11 (18%) partial responses (6 and 5, respectively); icORR – 24,6%. Progression has been documented in 4 patients (5,7%), 3 pts of them with previously treated BM. In all cases, progression occurred from the brain metastases. 2 pts have died (2,8%) before first assessment: on one of each group. Therapy with T-DXd was well tolerated, and no new safety signals were recorded. Adverse events were reported in 26 pts (37%). Pulmonitis Gr. 2 was recorded in 1 patient. The most common adverse events were nausea, asthenia, hepatotoxicity and thrombocytopenia, mainly Gr. 1-2. Conclusions: In real clinical practice therapy with T-DXd is highly effective in patients with ABM, including those previously irradiated. The therapy was well tolerated, no new data on AEs were received.