New Breast Cancer Drug T-DM1 Reveals Impressive Results For Patient’s Whose Cancer Has The HER2NEU Protein

 

New Breast Cancer Drug T-DM1 Reveals Impressive Results For Patient’s Whose Cancer Has The HER2NEU ProteinTrastuzumab Emtansine For HER2-positive Advanced Breast Cancer

Abstract

BACKGROUND:

Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate incorporating the human epidermal growth factor receptor 2 (HER2)-targeted antitumor properties of trastuzumab with the cytotoxic activity of the microtubule-inhibitory agent DM1. The antibody and the cytotoxic agent are conjugated by means of a stable linker.

METHODS:

We randomly assigned patients with HER2-positive advanced breast cancer, who had previously been treated with trastuzumab and a taxane, to T-DM1 or lapatinib plus capecitabine. The primary end points were progression-free survival (as assessed by independent review), overall survival, and safety. Secondary end points included progression-free survival (investigator-assessed), the objective response rate, and the time to symptom progression. Two interim analyses of overall survival were conducted.

RESULTS:

Among 991 randomly assigned patients, median progression-free survival as assessed by independent review was 9.6 months with T-DM1 versus 6.4 months with lapatinib plus capecitabine (hazard ratio for progression or death from any cause, 0.65; 95% confidence interval [CI], 0.55 to 0.77; P<0.001), and median overall survival at the second interim analysis crossed the stopping boundary for efficacy (30.9 months vs. 25.1 months; hazard ratio for death from any cause, 0.68; 95% CI, 0.55 to 0.85; P<0.001). The objective response rate was higher with T-DM1 (43.6%, vs. 30.8% with lapatinib plus capecitabine; P<0.001); results for all additional secondary end points favored T-DM1. Rates of grade 3 or 4 adverse events were higher with lapatinib plus capecitabine than with T-DM1 (57% vs. 41%). The incidences of thrombocytopenia and increased serum aminotransferase levels were higher with T-DM1, whereas the incidences of diarrhea, nausea, vomiting, and palmar-plantar erythrodysesthesia were higher with lapatinib plus capecitabine.

CONCLUSIONS:

T-DM1 significantly prolonged progression-free and overall survival with less toxicity than lapatinib plus capecitabine in patients with HER2-positive advanced breast cancer previously treated with trastuzumab and a taxane.

Dr. Chris’s Take:

I am so excited about this drug (Brand name: Kadycla). About 20% of breast cancer patients have a marker on their breast cancer cell called HER2NEU. This causes the breast cancer to take have more aggressive features. The drug Herceptin (traztuzumab) is now commonly used in stage 1-4 breast cancers to counteract the effects of this HER2NEU protein. Herceptin, however, tends to work best when given with chemotherapy (even though it can be given alone) which increases the side effects. Herceptin by itself has relatively few noticeable side effects. It is part of a class of drugs called targeted therapy meaning it targets something unique to the cancer cells not regular cells. This is unlike chemotherapy which is basically an atomic bomb that kills everything in its path but hopefully also kills the cancer cells as well. The drug above called T-DM1 is a drug combination of Herceptin and DM1. The Herceptin part of the drug attacks the HER2NEU protein and the DM1 then helps kills the cell. This is analogous to the Trojan Horse of Troy in ancient Greece. Remember, the horse hid the soldiers whom once inside the city of Troy were able to attack the city. T-DM1 in this study was given to patients whose cancer grew on Herceptin alone or with chemotherapy. It was also compared to another approved anti-HER2NEU combination Tykerb (lapatanib) and Xeloda (capecitabine. The survival with T-DM1 was clearly better than Tykerb and Xeloda and so much better tolerated with fewer side effects. I was involved in the original trials of this drug and have used it extensively. This drug is well tolerated and has impressive results. It has already been approved by FDA. However, it will be only approved for stage 4 cancer – cancer that has spread to another part of the body. However, all new drugs are approved for stage 4 cancers and then eventually work their way back to stages 1,2 and 3.

 

Resources: Trastuzumab emtansine for HER2-positive advanced breast cancer

Dr. Chris Charlton

Dr. Chris Charlton

Dr. Chris was born in Europe but has lived in the US for many years. He attended college both in Europe and the US and completed medical school at the University of Texas. Residency and fellowship in oncology was completed at Baylor. Read More...
Dr. Chris Charlton

Dr. Chris Charlton

Dr. Chris Charlton

Dr. Chris Charlton

Dr. Chris Charlton

Dr. Chris Charlton

Dr. Chris Charlton

Dr. Chris Charlton