進行乳がんに関する新たな治療法は有望である（Abstract # LBA1）

EMILIA：HER2-陽性進行乳がんの新たな治療法は現在の標準治療よりも無増悪生存期間を延長させる

EMILIA: New treatment for HER2-positive advanced breast cancer, improves progression-free survival over current standard therapies

治験薬トラスツズマブ-DM1（T-DM1）をカペシタビンとラパチニブ（XL）を用いた標準治療と比較した第3相無作為化スタディの結果、タキサンとトラスツズマブ治療歴を有するHER2陽性局所進行または転移性乳がん患者においてT-DM1による有意かつ臨床的に重要な無増悪生存期間（PFS）の改善が示された。EMILIAと呼ばれるこの国際スタディでは1,000人近くの患者をT-DM1 またはXLを疾患が増悪するかまたは対処不能な毒性が出現するまで3週ごとに施行する群に無作為に割り付けた。PFS中央値はT-DM1治療群で9.6か月であったのに対し、XL群では6.4か月であった－この差は統計学的に有意であった。2年後の生存率はT-DM1群で65.4%であったのに対し、XL群では47.5%であった。この統計的有意性における差はトライアルであらかじめ定義された一次解析用の統計学的生存率閾値に合致しなかった。スタディ後半で計画されている二次生存解析により、さらなる情報が提供されるであろう。T-DM1群におけるグレード3以上の一般的な有害事象は血小板減少（12.9%対0.2%）および肝機能検査値上昇であった。これらの副作用は休薬期間を設けることにより解決した。このスタディは2012年ASCO学会で発表された。

A phase III randomized study of the investigational agent trastuzumab emtansine (T-DM1) vs. standard therapy using capecitabine and lapatinib found significant and clinically meaningful improvement in progression-free survival (PFS) for T-DM1 in women with HER2-positive locally advanced or metastatic breast cancer previously treated with a taxane and trastuzumab. Results were presented at the American Society of Clinical Oncology's 48th Annual Meeting.

T-DM1 is an experimental antibody-drug conjugate that consists of the antibody trastuzumab linked to the cytotoxic drug emtansine (DM1).

"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, M.D., 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."

The international study, called EMILIA, randomized nearly 1,000 patients to receive either T-DM1 or XL every three weeks until their disease progressed or they experienced unmanageable toxicity.

The median PFS for patients receiving T-DM1 was 9.6 months, compared to 6.4 months in the group receiving capecitabine and lapatinib (a regimen known as XL) – a difference that was statistically significant.

After two years, 65.4 percent of the T-DM1 patients were alive, compared to 47.5 percent of the XL patients. This difference in statistical significance did not meet the trial's predetermined statistical survival threshold for the first analysis. The second survival analysis planned for later in the study will provide additional information.

The most common adverse events of Grade 3 or above for T-DM1 included thrombocytopenia (12.9 percent vs. 0.2 percent) and elevation in liver function tests. These side effects resolved when patients took a break from the drug, Dr. Blackwell said. Dose reductions were greater for patients in the XL group: 53.4 percent for capecitabine, 27.3 percent for lapatinib, and 16.3 percent for T-DM1.

Patients in the XL group experienced more diarrhea (20.7 percent vs. 1.6 percent), hand-foot syndrome (16.4 percent vs. 0), and vomiting (4.5 percent vs. 0.8 percent).