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Elsevier Global Medical News. 2011 Dec 21, B Jancin


SAN ANTONIO (EGMN) - Trastuzumab emtansine - the novel antibody-drug conjugate known as T-DM1 - provides significantly greater patient-reported quality of life and treatment tolerability than do standard trastuzumab and docetaxel in patients with previously untreated HER2-positive metastatic breast cancer, a phase II study indicates.

This is the same randomized, multicenter, open-label, phase II study that previously reported a highly significant 41% improvement in the efficacy end point of investigator-reported progression-free survival favoring trastuzumab emtansine by a margin of 14.2 months vs. 9.2 months, Dr. Giulia V. Bianchi noted at the annual San Antonio Breast Cancer Symposium.

Her new report presented key patient-reported outcomes, such as quality of life measurements. These data further define T-DM1 as a therapy that's superior to what's currently available, according to Dr. Bianchi of the Italian National Cancer Institute, Milan.

The primary patient-reported outcome was time to symptom progression (defined by at least a 5-point decrease from baseline on the Functional Assessment of Cancer Therapy-Breast Trial Outcome Index). Among 132 evaluable study participants, worsening of the FACT-B TOI score was significantly delayed in patients who were randomized to T-DM1; it occurred at a mean of 7.5 months in these patients, compared with 3.5 months in subjects assigned to trastuzumab (Herceptin) plus docetaxel (Taxotere).

The chief benefit of T-DM1 showed up on the physical well being subscale of the FACT-B TOI. Five of the seven items on the physical well-being subscale (lack of energy, feel ill, trouble meeting needs of family, bothered by side effects, and forced to spend time in bed) showed significantly better mean scores with T-DM1. The other two physical well-being items (nausea and pain) trended better in the T-DM1 group, but not significantly so.

The incidence of grade 3 or greater adverse events was 46% in the T-DM1 group vs. 89% in controls. Only 7% of patients in the T-DM1 arm stopped therapy because of adverse events, compared with 30% in the trastuzumab-plus-docetaxel arm.

Taken together, these data support the notion that T-DM1 is an advance in terms of tolerability, which in turn contributes to enhanced efficacy, safety, and health-related quality of life, Dr. Bianchi concluded.

The phase II study was sponsored by Genentech, which has big plans for T-DM1. The phase III MARIANNE trial, which is comparing T-DM1 as single-agent therapy with T-DM1 plus pertuzumab and with various trastuzumab/taxane combinations as first-line therapy in advanced HER2-positive breast cancer, is well underway. The phase III EMILIA trial is looking at T-DM1 for second-line use in advanced HER2-positive breast cancer. In addition, the monoclonal antibody and drug conjugate is under development for adjuvant and neoadjuvant use in early-stage breast cancer. T-DM1 is also being scrutinized as a potential treatment for HER2-positive gastric cancer.

Dr. Bianchi declared she has no financial conflicts of interest.

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