Efficacy and safety of trastuzumab emtansine (T-DM1) in patients with HER2-positive breast cancer with brain metastases

Abstract

Few data are currently available regarding the efficacy and safety of T-DM1 in breast cancer (BC) patients with unselected brain metastases (BM), since most clinical trials have excluded BM patients or have only included highly selected patients. HER2 + BC patients with BM treated with T-DM1 in 5 French centers were included in this retrospective study. Clinical management was performed according to the product guidelines. Efficacy was evaluated recording tumor response rates, progression-free (PFS) and overall survival, treatment compliance, and safety. Thirty nine patients received T-DM1, among whom 82 % presented with concomitant extra-cerebral disease. Median number of previous metastatic chemotherapy and HER2-directed targeted therapy regimens was 2 (range 0-8) and 1 (0-7), respectively. Thirty six patients had received BM loco-regional treatment (72 % whole-brain radiation therapy). After a median follow-up of 8.1 months (1.4-39.6), 24 patients had progressed (first site of progression: brain 14; meningeal 2; outside of the central nervous system 5; both intra- and extra-cerebral 3), 12 patients had died (disease progression), and 27 patients were still alive. Median number of T-DM1 cycles was 8 (1-43). There were 17 partial responses (44 %) and 6 patients achieved disease stabilization (59 % clinical benefit rate). Median PFS was 6.1 months (95 %CI 5.2-18.3), with one- and two-year PFS rates of 33 and 17 %, respectively. Treatment was well tolerated, without unexpected toxicities, treatment delay, or dose reduction. In this retrospective study, T-DM1 appeared to be an effective and well-tolerated therapeutic option in unselected HER2 + BC patients with BM. These findings require a prospective validation.

Development and responses of brain metastases during treatment with trastuzumab emtansine (T-DM1) for HER2 positive advanced breast cancer: A single institution experience

“…7 A recently published case series of 39 patients with brain metastases treated with T-DM1 reported a median time to brain progression of 8.6 months, with progression in the brain occurring as the first site of progression in 19 patients (48.7%), of whom only three had concurrent extra-cranial progression. 8 Similar to our study population, these patients had received a median of two prior lines of chemotherapy for advanced breast cancer, but in contrast, all patients had progressive brain disease when they commenced T-DM1. Despite this, their rate of brain progression on T-DM1 is similar to the rate (9/16, 56.3%) we report here in the 16 patients with known brain metastases, for whom the median brainspecific PFS was 9.9 months.…”

The prognosis analysis of different metastasis pattern in patients with different breast cancer subtypes: a SEER based study

“…However, in our study, we found that only the patients with HR-/HER2+ have a relatively better prognosis in brain metastasis. In fact, studies have shown that targeted drug herceptin can prolong the survival in breast cancer patients with brain metastases [27]. …”

Combination of Trastuzumab Emtansine and Stereotactic Radiosurgery Results in High Rates of Clinically Significant Radionecrosis and Dysregulation of Aquaporin-4

“…Systemic therapies including trastuzumab emtansine (T-DM1) can be effective in treating patients with HER2 þ breast cancer with central nervous system (CNS) disease, with T-DM1 showing improved median survival without increased risk for CNS progression compared with capecitabine-lapatinib in the EMILIA trial (6,7). Jacot and colleagues have also shown T-DM1 to be safe and effective in patients with HER2 þ breast cancer with brain metastases (8).…”