ASCO 2012 Report – T-DM1 improves progression free survival in breast cancer

by Marybeth Burke – The investigational agent trastuzumab emtansine (T-DM1) demonstrated improved efficacy over capecitibine plus lapatinib and improved progression-free survival (PFS) in women with HER2-positive locally advanced or metastatic breast cancer previously treated with a taxane and trastuzumab, according to a study released at the American Society of Clinical Oncology (ASCO) annual conference in Chicago in June.

“The drug worked.  It was significantly better than a very effective approved therapy for HER2 overexpressing metastatic breast cancer,” said lead study author Kimberly L. Blackwell, MD, professor of medicine and assistant professor of radiation oncology at Duke Cancer Institute at Duke University.  “Also, as a clinician who takes care of a lot of breast cancer patients, I’m pleased that this drug has very little dose-limiting toxicity.  Patients don’t lose their hair from this drug.  For patients facing metastatic breast cancer, this is a breakthrough,” Dr Blackwell added.

“T-DM1 is a new way of treating cancer…I think this will offer a very important therapeutic option,” she said.

At a later plenary session, discussant Louis M. Weiner, MD, Lombardi Comprehensive Cancer Center, Georgetown University, called “T-DM1 an important new weapon in the therapeutic armamentarium for breast cancer…the improved survival is particularly notable,” he told the audience.

EMILIA

T-DM1 is an antibody-drug conjugate comprising T, a stable linker, and the potent cytotoxic agent DM1.  It incorporates the antitumor activities of T and the HER2-targeted delivery of DM1, according Abstract #LBA1.

EMILIA is a randomized study of T-DM1 vs XL, the only approved combination for T-refractory HER2+MBC.  Patients received T-DM1 (3.6mg/kg IV q3w) or X (1000mg/m2 PO bid, days 1-14 q3w) + L (1250mg PO daily) until progressive disease (PD) or unmanageable toxicity, according to the abstract.

Patients had confirmed HER2 + MBC (IHC3+ and/or FISH+), and prior therapy with T and a taxane.  Primary endpoints were PFS by independent review, overall survival (OS) and safety.  An interim OS analysis was planned at the time of the final PFS analysis.

There were 978 patients who received treatment.  Median durations of follow-up were 12.9 (T-DM1) and 12.4 (XL) months.  Baseline demographics, prior therapy and disease characteristics were balanced.  “There was a significant improvement in PFS favouring T-DM1 (median 9.6 vs. 6.4 months; HR=0.650 [95% CI, 0.549-0771]; P<.0001),” according to the study.

The median T-DM1 OS was not reached vs. 23.3 months (HR=0.621 [95% CI, 0.475-0.813]; P=.0005; the interim efficacy boundary was not crossed.  T-DM1 was well tolerated.  The most common Grade ³3 adverse events per treatment were for T-DM1: thrombocytopenia (12.9% vs 0.2%, increased AST (4.3% vs 0.8%), and increased ALT (2.9% vs1.4%); for XL: diarrhoea (20.7% vs 1.6%), palmar plantar erythrodysesthesia (16.4% vs 0) and vomiting (4.5% vs 0.8%).

Dose reductions were greater for patients in the XL group: 53.4% for capecitabine, 27.3% for lapatinib, and 16.3% for T-DM1.

Dr Weiner said that T-DM1 merits evaluation possibly for the early stages of the disease and “raises many new avenues for exploration.”