The efficacy of sacituzumab govitecan and trastuzumab deruxtecan on stable and active brain metastases in metastatic breast cancer patients-a multicenter real-world analysis

Abstract

Background: Fifteen to thirty percent of all patients with metastatic breast cancer (MBC) develop brain metastases (BCBMs). Recently, the antibody-drug conjugates (ADCs) sacituzumab govitecan (SG) and trastuzumab deruxtecan (T-DXd) have shown to be highly effective in the treatment of MBC. However, there are only limited data whether these macromolecules are also effective in patients with BCBMs. We therefore aimed to examine the efficacy of SG and T-DXd in patients with stable and active BCBMs in a multicenter real-world analysis.

Patients and methods: Female patients with stable or active BCBMs who were treated with either SG or T-DXd at three breast centers in Germany before 30 June 2023 were included. As per local clinical praxis, chemotherapy efficacy was evaluated by whole-body computed tomography and cranial magnetic resonance imaging at baseline and at least every 3 months according to local standards. Growth dynamics of BCBMs were assessed by board-certified neuroradiologists.

Results: Of 26 patients, with a median of 2.5 prior therapy lines in the metastatic setting (range 2-15), 12 (43%) and 16 (57%) patients received SG and T-DXd, respectively. Out of the 12 patients who received SG, 2 (17%) were subsequently treated with T-DXd. Five out of 12 (42%) and 5 out of 16 (31%) patients treated with SG and T-DXd, respectively, had active BCBMs at treatment initiation. The intracranial disease control rate was 42% [95% confidence interval (CI) 13% to 71%] for patients treated with SG and 88% (95% CI 72% to 100%) for patients treated with T-DXd. After a median follow-up of 12.7 months, median intracranial progression-free survival was 2.7 months (95% CI 1.6-10.5 months) for SG and 11.2 months (95% CI 7.5-23.7 months) for T-DXd.

Conclusions: SG and T-DXd showed promising clinical activity in both stable and active BCBMs. Further prospective clinical studies designed to investigate the efficacy of modern ADCs on active and stable BCBMs are urgently needed.

Keywords: antibody–drug conjugates; brain metastasis; breast cancer; real-world data.

Figure 1

Breast cancer patients with BCBMs were treated with either sacituzumab govitecan (green) or trastuzumab deruxtecan (purple)for a specified number of days, and icPFS was observed. Sequential treatment using both drugs was also a viable option. If the therapy ended before an icPFS event occurred, the interval without ADC application is indicated by black hatching. An icPFS event is denoted by a red sickle. Therapy cessation due to extracranial disease progression is indicated by the letter ‘X’. Therapy cessation due to treatment-emergent adverse events is indicated by the letter ‘A’. Therapy cessation due to patients’ wish is indicated by the letter ‘P’. Continued treatment is indicated by a red triangle, and patient death is indicated by a cross. Patients who underwent radiation therapy before or during ADC treatment are identified by a yellow lightning bolt. Patients with an HER2-low status are labeled as ‘low.’ ADC, antibody–drug conjugate; BCBMs, breast cancer brain metastases; icPFS, intracranial progression-free survival.

Figure 2

Intracranial progression-free survival and overall survival for patients receiving SG. (A) icPFS of patients with BCBMs who received treatment with SG. (B) icPFS of patients diagnosed with active and stable BCBMs. (C) OS of patients with BCBMs who received treatment with SG. (D) OS of patients diagnosed with active and stable BCBMs. BCBMs, breast cancer brain metastases; icPFS, intracranial progression-free survival; OS, overall survival; SG, sacituzumab govitecan.

Figure 3

Intracranial progression-free survival and overall survival for patients receiving T-DXd. (A) icPFS of patients with BCBMs who received treatment with T-DXd. (B) icPFS of patients diagnosed with active and stable BCBMs. (C) OS of patients with BCBMs who received treatment with T-DXd. (D) OS of patients diagnosed with active and stable BCBMs. BCBMs, breast cancer brain metastases; icPFS, intracranial progression-free survival; OS, overall survival; T-DXd, trastuzumab deruxtecan.