EMILIA: T-DM1 Demonstrates Greater Safety, Efficacy for Advanced HER2-Positive Breast Cancer

The highly anticipated results of the EMILIA study, a phase III trial of trastuzumab emtansine (T-DM1) compared with capecitabine plus lapatinib, were presented by Kimberly L. Blackwell, MD, of Duke Cancer Institute, at Sunday’s Plenary Session (Abstract LBA1).

T-DM1 is a three-part immunoconjugate consisting of trastuzumab, a stable linker, and the potent maytansine derivative, DM1. This new compound incorporates the antitumor activity of trastuzumab with its ability to deliver a microtubule disrupting cytotoxic agent specifically to antigen-expressing tumor cells.

Patients previously treated with a taxane and trastuzumab were eligible for the study if they had progressive disease during treatment for metastases or had recurrent disease within 6 months of adjuvant therapy. Stratification factors included world region, number of prior chemotherapy regimens, and presence of visceral disease.

Although 991 were enrolled, 978 patients were treated in the study. Median dose intensity was 99.9% for those receiving T-DM1, 77.2% for those receiving capecitabine, and 93.4% for those treated with lapatinib. Dose reduction was necessary for only 16.3% of patients in the T-DM1 arm; however, the capecitabine dose and the lapatinib dose had to be reduced for 53.4% and 27.3% of patients, respectively.

Median progression-free survival was 9.6 months in the T-DM1 arm compared with 6.4 months in the capecitabine/ lapatinib arm (stratified hazard ratio [HR] = 0.650, 95% CI: 0.55–0.77; p < 0.0001, Figure).

Subgroup analyses according to baseline characteristics indicated that T-DM1 was better for all groups except for those patients ages 65 and older. Overall survival was improved for patients receiving T-DM1, but median overall survival has not been reached for these patients and the efficacy boundary has not been crossed. The objective response rate was significantly higher in the T-DM1 group at 43.6% compared with 30.8% in the capecitabine/lapatinib group (95% CI: 6.0–19.4, p = 0.0002).

T-DM1 was much safer than capecitabine/lapatinib. Median time to symptom progression was 7.1 months in the T-DM1 group and 4.6 months in the capecitabine/lapatinib group (HR = 0.80, 95% CI: 0.67–0.95, p = 0.0121).

The incidence of grade 3 or higher severe adverse events was lower in the T-DM1 group (40.8%) than in the capecitabine/lapatinib group (57.0%), as was the incidence of adverse events resulting in treatment discontinuation (5.9% vs. 10.7%, respectively). Cardiac toxicity was not increased. There was one death due to toxicity in the T-DM1 group and five in the capecitabine/lapatinib group.

Dr. Blackwell concluded that T-DM1 demonstrated greater efficacy and safety than capecitabine/lapatinib and that T-DM1 should offer an important therapeutic option for the treatment of HER2-positive advanced breast cancer.

In his discussion, Louis M. Weiner, MD, of Georgetown Lombardi Comprehensive Cancer Center, stated that the EMELIA study provides convincing evidence that an immunoconjugate-targeting HER2 has potent antitumor activity, referring to immunoconjugates as the realization of Paul Ehrlich’s concept of a "magic bullet" developed more than 100 years ago.