Activity of T-DM1 in Her2-positive breast cancer brain metastases

Abstract

Brain metastases (BM) are frequently diagnosed in metastatic Her2-positive breast cancer. Local treatment remains the standard of care but lapatinib plus capecitabine was recently established as systemic therapy option. Due to a disruption of the blood-brain/tumour-barrier at metastatic sites, even large molecules may penetrate into the central nervous system (CNS). Here, we report on the activity of T-DM1 in Her2-positive breast cancer BM. T-DM1 was administered at a dose of 3.6 mg once every 3 weeks as primary systemic therapy for BM or upon documented CNS progression after initial local treatment. Thus, this study allowed for the appraisal of T-DM1 activity in BM. Restaging was conducted every 12 weeks with MRI or whenever symptoms of disease progression occurred. Ten patients were included; in two asymptomatic subjects, T-DM1 was administered as primary therapy, while eight had progressive BM. All patients had received prior treatment with trastuzumab, six had already received lapatinib, and three pertuzumab as well. Three patients had partial remission of BM, and two patient had stable disease lasting for ≥6 months; two further patients had stable disease for <6 months while three progressed despite treatment. At 8.5 months median follow-up, intracranial PFS was 5 months, and median OS from initiation of T-DM1 was not reached. Local treatment of BM remains the standard of care; lapatinib plus capecitabine is currently the best established systemic therapy option. Still, T-DM1 apparently offers relevant clinical activity in BM and further investigation is warranted.

Diagnosis and treatment of brain metastases from solid tumors: guidelines from the European Association of Neuro-Oncology (EANO)

“…88 Several case reports and small patient series indicate that the antibody-drug conjugate T-DM1 (trastuzumab emtansine) may be active against brain metastases of HER2+ breast cancer (class IV). 89,90 Few data only are available on the combination of different anti-HER2 agents. There are no reliable data on the efficacy of endocrine therapies.…”

Brain metastasis: Unique challenges and open opportunities

“…While several targeted therapies do indeed show activity in the brain and are delivered into the brain metastatic tumors, their accumulation in the brain generally occurs at dramatically lower concentrations than outside the brain [24], raising the question of whether efficacious concentrations of the drugs are ever reached or maintained. One notable and recent exception is the antibody-drug conjugate ado-trastuzumab emtansine (T-DM1), which targets HER2 in HER2-overexpressing breast cancer; T-DM1 has shown clinical efficacy in HER2+ brain metastasis both as a single agent and in combination, positively impacting both progression-free and overall survival [25, 26]. Yet even in patients showing responses to T-DM1, the metastases ultimately relapse.…”

Systemic Treatment Options for HER2-Positive Breast Cancer Patients with Brain Metastases beyond Trastuzumab: A Literature Review

“…The second cohort, published by Bartsch et al [7], evaluated the efficacy of T-DM1 in 10 patients with BM of breast cancer and trastuzumab pretreatment. An intracranial PFS of 5 months was observed; 3 patients had partial remission of BM, 4 had stable disease, and 3 progressed under the treatment.…”