Elsevier

Annals of Oncology

Volume 26, Issue 1, January 2015, Pages 113-119
Annals of Oncology

original articles
breast tumors
Trastuzumab emtansine (T-DM1) versus lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer and central nervous system metastases: a retrospective, exploratory analysis in EMILIA

https://doi.org/10.1093/annonc/mdu486Get rights and content
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open access

ABSTRACT

Background

We characterized the incidence of central nervous system (CNS) metastases after treatment with trastuzumab emtansine (T-DM1) versus capecitabine–lapatinib (XL), and treatment efficacy among patients with pre-existing CNS metastases in the phase III EMILIA study.

Patients and methods

In EMILIA, patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer previously treated with trastuzumab and a taxane were randomized to T-DM1 or XL until disease progression. Patients with treated, asymptomatic CNS metastases at baseline and patients developing postbaseline CNS metastases were identified retrospectively by independent review; exploratory analyses were carried out.

Results

Among 991 randomized patients (T-DM1 = 495; XL = 496), 95 (T-DM1 = 45; XL = 50) had CNS metastases at baseline. CNS progression occurred in 9 of 450 (2.0%) and 3 of 446 (0.7%) patients without CNS metastases at baseline in the T-DM1 and XL arms, respectively, and in 10 of 45 (22.2%) and 8 of 50 (16.0%) patients with CNS metastases at baseline. Among patients with CNS metastases at baseline, a significant improvement in overall survival (OS) was observed in the T-DM1 arm compared with the XL arm [hazard ratio (HR) = 0.38; P = 0.008; median, 26.8 versus 12.9 months]. Progression-free survival by independent review was similar in the two treatment arms (HR = 1.00; P = 1.000; median, 5.9 versus 5.7 months). Multivariate analyses demonstrated similar results. Grade ≥3 adverse events were reported in 48.8% and 63.3% of patients with CNS metastases at baseline administered T-DM1 and XL, respectively; no new safety signals were observed.

Conclusion

In this retrospective, exploratory analysis, the rate of CNS progression in patients with HER2-positive advanced breast cancer was similar for T-DM1 and for XL, and higher overall in patients with CNS metastases at baseline compared with those without CNS metastases at baseline. In patients with treated, asymptomatic CNS metastases at baseline, T-DM1 was associated with significantly improved OS compared with XL.

ado-trastuzumab emtansine
T-DM1
metastatic breast cancer
central nervous system metastasis

Cited by (0)

These data were presented in part at: The 36th Annual San Antonio Breast Cancer Symposium; San Antonio, TX, USA; 10–14 December 2013. I. Krop, N. Lin, K. Blackwell et al. Efficacy and safety of trastuzumab emtansine (T-DM1) versus lapatinib plus capecitabine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer and central nervous system metastases: results from a retrospective exploratory analysis of EMILIA.

Present Address: Department of Gynecology, University of Ulm, Ulm, Germany.