Study of the Efficacy and Safety of Stereotactic Radiation Therapy in Combination with Trastuzumab Emtansine Immunoconjugate in Patients with HER-2-positive Oligometastatic Breast Cancer. Interim Results

Abstract

Introduction. Proposed by S. Hellman and R. Weichselbaum in 1995, the concept of oligometastatic disease represents a fundamentally new approach to understanding the extent of tumor spread. Combining systemic therapy (chemotherapy, immunotherapy and targeted therapy) with local treatment methods is an important area of modern scientific research. Further study is required into a combination approach involving the use of anti-HER2 therapy with trastuzumab emtansine (TDM-1) 24 h after stereotactic ablative radiation therapy (SABR) for oligometastases (OM).

Aim. To evaluate the efficacy and safety of SABR in combination with the antibody-drug conjugate TDM-1, 24 h after the completion of SABR, in patients with HER2-positive oligometastatic breast cancer (HER2+OMBC).

Materials and methods. From July 2022 to November 2024, 49 patients with HER2 + OMBC were enrolled in this study. In the first stage, all patients underwent SABR to target accessible OM, followed by the administration of TDM-1, 24 hours post-SRT. In the second stage, TDM-1 drug therapy (three cycles) was conducted at the N.N. Petrov National Medical Research Center of Oncology, continuing until progression or intolerable toxicity according to recommendations of the Ministry of Health of Russia. The primary endpoint was the objective response rate (ORR). The secondary endpoints were progression-free survival (PFS) and the incidence of adverse events (AEs).

Results. The efficacy and toxicity analysis included data from 42 patients, with a mean age of 52 years (range 36–75). The average number of OM per patient was 4 (range 1–5). One-third of the patients had oligometastatic brain involvement (n = 14), while the remaining patients had extracranial lesions (n = 28), located in the lungs (n = 4), bones (n = 2), liver (n = 1) and other sites (n = 21). At a median follow-up of 12 months, the overall response rate (ORR) was 52.4%, while the disease control rate (DCR) was 90.5%. The six-month and one-year PFS rates were both 100%. The most common adverse event during combination therapy was mild to moderate hepatotoxicity (30.9 %), which was comparable to registration study data for TDM-1 drug. However, the incidence of pneumonitis in our study (9.5%) was twice that reported in the EMILIA trial, possibly due to SABR being applied to thoracic OM.

Conclusion. A high level of disease control (90.5%, with 52.4% OR and stabilization of the process) and 100% six-month and one-year PFS under moderate toxicity levels indicate significant potential for the combined treatment of HER2+OMBC. A longer observation period is necessary to fully understand the long-term effects and safety of SABR on accessible OM followed by the administration of TDM-1 24 h after radiation therapy until progression or unacceptable toxicity.