(CHICAGO, IL) – The experimental agent trastuzumab emtansine (T-DM1) offers significant and “clinically meaningful” improvement in progression free survival (PFS) among women with HER2-positive locally advanced or metastatic breast cancer who previously received a taxane and trastuzumab (Herceptin), according to a randomized phase 3 study reported upon at the 2012 American Society of Clinical Oncology Annual Meeting.

“This drug is significantly better than the current approved combination in keeping the cancer under control,” said lead author Kimberly L. Blackwell, MD, Processor of medicine and assistant professor of radiation oncology at Duke University Medical Center, Durham, NC. “This is a drug that brings us another step closer to treating cancer without the side effects of chemotherapy. It’s going to be a good option for patients faced with HER2-positive tumors.”

T-DM1 is an experimental antibody-drug conjugate agent composed of trastuzumab linked to the cytotoxic chemotherapy drug emtansine (DM1); Joining trastuzumab directly to DM1 allows targeted delivery of DM1 to HER2-expressing tumor tissue. T-DM1 has not been approved by the Food and Drug Administration (FDA) and is not yet available outside of clinical trials.

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The international EMILIA study randomized 991 patients with HER2+ metastatic breast cancer and prior therapy with trastuzumab and taxane, to receive either T-DM1 (3.6mg/kg IV every three weeks) or capecitabine (1000mg/m2 orally twice daily on Days 1-14 every three weeks) + lapatinib (1250mg orally daily) until disease progression or unmanageable toxicity.

The primary end point PFS was significantly longer in T-DM1 patients after a median follow-up of 12.9 months (median PFS 9.6 vs 6.4 months; HR=0.65;P<0.0001; subgroup analysis showed that patients > 65 years of age did not have a significant improvement in PFS as the whole population. Secondary end points OS and ORR were also improved in the T-DM1.The most common grade 3/4 adverse events for T-DM1 were thrombocytopenia (12.9% vs 0.2%), and elevations in liver function tests (increased AST 4.3% vs 0.8% and ALT 2.9% vs 1.4%). In general, 57% of placebo had AEs vs 43% in TDM1. These toxicities resolved when T-DMI administration was interrupted, Dr. Blackwell said. Dose reductions occurred in 16.3% of patients in the T-DMI-arm vs 53.4% for capecitabine and 27.3% for lapatinib.

TDM1 demonstrated improved efficacy over capecitabine plus lapatinib; safety and secondary efficacy also favored TDM1, investigators concluded.