Ado-trastuzumab emtansine significantly extended OS in HER-2–positive breast cancer with CNS metastases

Patients with HER-2–positive advanced breast cancer treated with ado-trastuzumab emtansine experienced similar rates of central nervous system progression as those treated with capecitabine plus lapatinib, according to study results.

However, among patients with treated, asymptomatic central nervous system (CNS) metastases at baseline, those assigned the antibody–drug conjugate ado-trastuzumab emtansine (Kadcyla, Genentech) experienced significantly longer OS than those assigned capecitabine plus lapatinib (Tykerb, GlaxoSmithKline).

Ian E. Krop, MD, of the department of medical oncology at Dana-Farber Cancer Institute and Harvard University School of Medicine, and colleagues conducted a retrospective, exploratory analysis of data from the phase 3 EMILIA study.

The EMILIA study included 991 patients with HER-2–positive advanced breast cancer who underwent previous treatment with trastuzumab (Herceptin, Genentech) and a taxane. Researchers randomly assigned 495 patients to ado-trastuzumab emtansine, and the other 496 received capecitabine plus lapatinib. Treatment continued until disease progression.

Researchers retrospectively identified patients with treated, asymptomatic CNS metastases at baseline, as well as those who developed post-baseline CNS metastases.

Krop and colleagues determined 95 patients — 45 assigned to ado-trastuzumab emtansine, and 50 assigned to capecitabine plus lapatinib — had CNS metastases at baseline.

Among patients without CNS metastases at baseline, CNS progression occurred in nine patients (2%) assigned ado-trastuzumab emtansine and three patients (0.7%) assigned capecitabine plus lapatinib. Among patients with CNS metastases at baseline, CNS progression occurred in 10 patients (22.2%) assigned ado-trastuzumab emtansine and eight patients (16%) assigned capecitabine plus lapatinib.

Among patients with CNS metastases at baseline, those treated with ado-trastuzumab emtansine experienced significantly longer median OS than those treated with capecitabine plus lapatinib (26.8 months vs. 12.9 months; HR=0.38; P=.008). Median PFS was comparable between arms (5.9 months vs. 5.7 months; HR=1; P=1).

Multivariate analyses confirmed the survival outcomes.

Among those with CNS metastases at baseline, grade ≥3 adverse events occurred in 48.8% of those treated with ado-trastuzumab emtansine and 63.3% of those treated with capecitabine plus lapatinib.