Gastrointestinal Cancer Section, City of Hope National Medical Center, Duarte, California, USA
Oncologist. 2018 Apr;23(4):474-477. doi: 10.1634/theoncologist.2017-0436. Epub 2018 Jan 12.
Human epidermal growth factor 2 (HER2) amplification represents a distinct molecular subgroup of colorectal cancers that is associated with anti-epidermal growth factor receptor resistance and sensitivity to dual HER2 targeting. Although clinical trials have reported activity for trastuzumab/pertuzumab and trastuzumab/lapatinib combinations, there are no reports on lapatinib plus trastuzumab activity after resistance to trastuzumab plus pertuzumab. Presented are three cases of HER2 amplified colorectal cancer that developed acquired refractoriness to trastuzumab pertuzumab with subsequent clinical benefit to lapatinib plus trastuzumab, highlighting the potential for HER2 tyrosine kinase inhibition plus trastuzumab in overcoming trastuzumab/pertuzumab resistance.
人表皮生长因子 2（HER2）扩增代表结直肠癌的一个独特分子亚群，与抗表皮生长因子受体耐药性以及对双 HER2 靶向治疗的敏感性相关。虽然临床试验报道了曲妥珠单抗/帕妥珠单抗和曲妥珠单抗/拉帕替尼联合应用的活性，但尚无曲妥珠单抗加培妥珠单抗耐药后使用拉帕替尼加曲妥珠单抗活性的报告。本文报告了三例 HER2 扩增的结直肠癌患者，这些患者对曲妥珠单抗培妥珠单抗产生获得性耐药，随后使用拉帕替尼加曲妥珠单抗获得临床获益，突出了 HER2 酪氨酸激酶抑制剂联合曲妥珠单抗克服曲妥珠单抗/培妥珠单抗耐药的潜力。
