Horinouchi Hidehito
a Department of Thoracic Oncology , National Cancer Center Hospital , Tokyo , Japan.
b Advanced Clinical Research of Cancer , Juntendo University Graduate School of Medicine , Tokyo , Japan.
Expert Opin Biol Ther. 2016 Dec;16(12):1549-1555. doi: 10.1080/14712598.2016.1249846. Epub 2016 Nov 3.
The mutation or expression of HER family members serves as a therapeutic target for tyrosine kinase inhibitors or monoclonal antibodies in diverse cancers, such as non-small cell lung cancer, breast cancer, gastric cancer, head and neck cancer, colorectal cancer, pancreatic cancer and glioblastoma. HER3, which heterodimerizes with HER1 and HER2, has received much attention as a potential target for anti-EGFR treatment. Patritumab is a novel, fully human monoclonal antibody directed against HER3. Areas covered: In this review article, an overview of the market, chemistry, pharmacodynamics, pharmacokinetics, efficacy, and safety of patritumab is provided based on data from phase I studies, a combination phase I trial, and a randomized phase II trial comparing two doses of patritumab. Expert opinion: The combination of patritumab plus erlotinib has shown a promising efficacy and safety in early-phase clinical trials. In a randomized phase II trial, higher mRNA expression of heregulin (a ligand of HER3) was associated with better progression-free survival and a tendency toward improved overall survival. In the era of precise treatment based on an appropriate target with a predictive biomarker, further studies with patritumab are needed to realize its potential in cancer treatment.
HER家族成员的突变或表达是多种癌症中酪氨酸激酶抑制剂或单克隆抗体的治疗靶点,如非小细胞肺癌、乳腺癌、胃癌、头颈癌、结直肠癌、胰腺癌和胶质母细胞瘤。HER3与HER1和HER2形成异源二聚体,作为抗EGFR治疗的潜在靶点备受关注。帕妥珠单抗是一种新型的、完全人源化的抗HER3单克隆抗体。涵盖领域:在这篇综述文章中,基于I期研究、I期联合试验以及比较两剂帕妥珠单抗的随机II期试验数据,对帕妥珠单抗的市场、化学、药效学、药代动力学、疗效和安全性进行了概述。专家观点:帕妥珠单抗联合厄洛替尼在早期临床试验中显示出有前景的疗效和安全性。在一项随机II期试验中,这里调节蛋白(HER3的一种配体)的较高mRNA表达与更好的无进展生存期以及总生存期改善趋势相关。在基于合适靶点和预测性生物标志物的精准治疗时代,需要对帕妥珠单抗进行进一步研究以实现其在癌症治疗中的潜力。