HER2-positive Metastatic Breast Cancer: New Agents on the Horizon
W Yeo
Hong Kong J Radiol 2012;15(Suppl):S51-6
The human epidermal growth factor receptor HER2/neu gene is amplified and overexpressed in 25 to 30% of breast cancers. In women with HER2-positive advanced or metastatic breast cancer, the anti-HER2 monoclonal antibody trastuzumab and the dual tyrosine kinase inhibitor lapatinib are both established options used in combination with cytotoxic chemotherapy. In patients who progress after first-line therapy with trastuzumab plus chemotherapy, continued trastuzumab or switching to lapatinib, both in combination with cytotoxic chemotherapy, offers clinical benefit. New agents in the metastatic disease setting include pertuzumab and trastuzumab emtansine. In the first-line setting, the addition of pertuzumab to trastuzumab/docetaxel yields longer median progression-free survival than placebo plus trastuzumab/docetaxel (18.5 vs. 12.4 months; p < 0.001). In the second-line setting, trastuzumab emtansine alone improves median progression-free survival compared with capecitabine plus lapatinib (9.6 vs. 6.4 months; p < 0.0001). The combination of trastuzumab emtansine plus pertuzumab has also shown encouraging preliminary activity. Other agents in clinical development include subcutaneous trastuzumab, afatinib, and neratinib. Numerous other treatments across a range of drug classes are currently in development for the treatment of HER2-positive metastatic breast cancer.
中文摘要
HER-2陽性轉移性乳癌：現有的新製劑
楊明明
25%至30%的乳癌有人類表皮生長因子受體2（HER2）／neu基因放大和過度表現的情況。晚期或轉 移性HER-2陽性乳癌的患者中，抗HER2單株抗體trastruzumab以及雙酪胺酸激酶抑制劑lapatinib，都 是可以結合細胞毒性化療的已知選擇。對於接受trastruzumab和化療的第一線治療後仍有惡化的患 者，繼續trastruzumab治療或者改為lapatinib治療，而再結合化療，可以有臨床上的好處。治療轉移 性乳癌的新製劑包括有pertuzumab和trastuzumab emtansine。第一線治療中，與沒有加入pertuzumab 的治療比較，在trastuzumab/docetaxel加入pertuzumab會有較長的無惡化存活期中位數（前者為12.4 個月，後者為18.5個月；p < 0.001）。第二線治療中，與capecitabine結合lapatinib的治療比較， trastuzumab emtansine可改善無惡化存活期中位數（前者為6.4個月，後者為9.6個月；p < 0.0001）。結 合trastuzumab emtansine及pertuzumab的治療在初步試驗中出現鼓舞性的結果。其他製劑包括作皮下注 射的trastuzumab、afatinib和neratinib正處於臨床研究階段。目前正開發許多針對HER-2陽性轉移性乳 癌的一系列藥物治療。