T-DM1 Increases the Risk of SRS-Induced Radiation Necrosis in Her2+ Breast Cancer.

PURPOSE/OBJECTIVE(S): Stereotactic radiosurgery (SRS) is an important treatment modality in the management of breast cancer-related brain metastases (BrM). Recent research has found Trastuzumab emtansine (T-DM1) to be effective against Her2+ BrM. However, the risk of radionecrosis (RN) with T-DM1 in combination with SRS is unclear. The objective of this study was to investigate factors associated with RN post-SRS in patients with Her2+ BrM.

MATERIALS/METHODS: Patients with Her2+ BrM treated with SRS at the Sunnybrook Odette Cancer Centre between 2010 and 2020 were retrospectively identified. The incidence of RN was determined on a lesion-by-lesion basis using serial brain imaging with or without histological confirmation. Clinical factors associated with RN, such as age, RT dose, lesion volume, intracranial location, total number of BrM, along with history of whole brain RT, and T-DM1 treatment were investigated with univariable and multivariable competing risks regression (MVR) using death from any cause as a competing risk factor. A P-value of < 0.05 in MVR following backward selection was considered statistically significant.

RESULTS: 67 patients with Her2+ BrM (223 lesions) treated with SRS were identified; among them, 21 (31.3%) were treated with T-DM1 post-SRS, including 14 (20.9%) who received T-DM1 within 12 months of SRS. The median follow-up was 15.6 (IQR 5.4-35.3) months. The 1-year, and 2-year risk of RN post-SRS was 6.7% (95% CI 2.7-10.7%), and 15.2% (95% CI 9.2-21.3%), respectively. MVR identified T-DM1 treatment post-SRS (HR 2.5, 95% CI 1.2-5.3, P = 0.02) and RT dose with a biologically effective dose (BED) > 50.4 Gy (HR 2.4, 95% CI 1.1-5.1, P = 0.02) as independent risk factors of RN. Patients treated with T-DM1 and SRS had a 25.2% (95% CI 12.8-37.6%) risk of RN at both 1- and 2-years post-T-DM1. The median time to RN after T-DM1 among the affected was 4.8 (95% CI: 3.8-25.6) months with 80% of all RN cases occurring within 12 months of T-DM1 treatment.

CONCLUSION: This study demonstrates that T-DM1 exposure post-SRS was independently associated with a higher risk of RN in Her2+ BrM patients. The potential side effects of brain-penetrating agents post-SRS merit greater awareness.

AUTHOR DISCLOSURE: B. Id Said: None. H. Chen: None. K. Jerzak: Research Grant; Astra Zeneca, Eli Lilly. Consultant; Amgen, AstraZeneca, Apo Biologix, Eli Lilly, Esai, Genomic Health, Knight Therapeutics, Merck, Myriad Genetics Inc, Pfizer, Roche, Novartis, Purdue Pharma. S.D. Myrehaug: Advisory Board; Novartis AG.C. Tseng: Consultant; Sanofi. Travel Expenses; Elekta. Member; Elekta MR-LINAC.J. Detsky: None. Z.A. Husain: None. A. Sahgal: Research Grant; Elekta AB. Honoraria; Elekta AB, Varian, BrainLAB, Medtronic Kyphon. Consultant; Varian. Travel Expenses; Elekta AB, Varian. H. Soliman: None.