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Abstract
Introduction. The concept of oligometastatic disease (OMD) marked a paradigm shift in the understanding of the metastatic process. In the current scientific agenda, studying the efficacy of combining systemic treatments with local ablative methods occupies an important place. The combined approach of initiating trastuzumab emtansine (T‑DM1) anti‑HER2 therapy 24 hours after completing stereotactic radiotherapy (SRT) to oligometastases requires further investigation.
Aim. To evaluate the efficacy of a combined treatment approach utilizing SRT followed by T-DM1 in patients with HER2-positive oligometastatic breast cancer (HER2+ OMBC).
Materials and Methods. The study included 175 patients with HER2+ metastatic breast cancer (mBC) treated with T-DM1 at the N.N. Petrov National Medical Research Center of Oncology (2019–2025). Patients were stratified into 4 groups based on the presence and timing of SRT. The samples were comparable (p > 0.05) and representative. The primary endpoint was objective response rate (ORR); secondary endpoints were progression-free survival (PFS) and adverse events (AEs).
Results. The highest ORR (52.4%) was observed in Group 1. Increasing the interval between local therapy (SRT) and the initiation of systemic treatment to ≥30 days reduced the ORR to 15.4%. In the groups that did not receive SRT (Groups 3 and 4), the ORR was 14.2% and 12.1%, respectively. A 24-hour interval reduction significantly improved PFS: 6-month PFS was 100% compared to 81.3% in the group with a ≥30-day interval, and 1-year PFS was 100% versus 55% (OR 0.20; 95% CI 0.09–0.51; p<0.001). Predictors of superior PFS: SRT administration (OR 0.14; 95% CI 0.05–0.36; p<0.001) and T-DM1 initiation 24 hours post-SRT (OR 0.33; 95% CI 0.13–0.85; p=0.022).
Conclusion. The promising disease control rate of 90.5%, combined with 100% PFS rates at both 6 and 12 months, along with an acceptable toxicity profile, indicate the potential of the proposed combined-modality strategy for HER2+ OMBC. Final assessment of long-term outcomes and confirmation of the safety of the combined approach require prolonged follow-up of the patient cohort.
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