Guan Ji-Lin, Liu Jian-Hua, Wang Qing, Cong Yu-Wei, Chen Yao-Xu, Huang Ke-Fei, Huang Meng-Li, Huang Ling
Department of Oncology, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou 510655, Guangdong Province, China.
The Medical Department, 3D Medicines Inc., Shanghai 201114, China.
World J Gastrointest Oncol. 2020 Sep 15;12(9):1065-1072. doi: 10.4251/wjgo.v12.i9.1065.
Human epidermal growth factor receptor 2 (HER2) amplification is a molecular driver for a subset of colorectal cancers (CRCs) and one of the major causes of anti-epidermal growth factor receptor (EGFR) treatment failure. Compared to dual anti-HER2 treatments, which have been shown to be effective in HER2-positive metastatic CRC patients, single-agent anti-HER2 therapy is rarely used to treat CRC.
Herein, we report a case of RAS/BRAF-wild-type metastatic CRC that was identified as HER2-positive through circulating tumor DNA (ctDNA) testing by next-generation sequencing following the failure of two lines of therapy. Subsequently, the patient was given lapatinib monotherapy that led to a partial response with a progression-free survival of 7.9 mo. Moreover, serial ctDNA detection was used to monitor the efficacy of lapatinib. The aberration of HER2 copy number disappeared when radiographic assessment revealed a partial response. However, a high level of HER2 amplification was detected again at the time of disease progression. Finally, a phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha mutation was identified at the time of tumor progression, which may explain the acquired resistance to lapatinib.
This is the first case report of HER2-positive RAS/BRAF wild-type metastatic CRC patient responding to lapatinib monotherapy. It highlights that ctDNA testing is an effective and feasible approach to evaluate the efficacy of anti-HER2 therapy.
人表皮生长因子受体2（HER2）扩增是一部分结直肠癌（CRC）的分子驱动因素，也是抗表皮生长因子受体（EGFR）治疗失败的主要原因之一。与已被证明对HER2阳性转移性CRC患者有效的双联抗HER2治疗相比，单药抗HER2治疗很少用于治疗CRC。
在此，我们报告一例RAS/BRAF野生型转移性CRC病例，该病例在两线治疗失败后通过下一代测序的循环肿瘤DNA（ctDNA）检测被鉴定为HER2阳性。随后，该患者接受拉帕替尼单药治疗，产生部分缓解，无进展生存期为7.9个月。此外，采用连续ctDNA检测来监测拉帕替尼的疗效。当影像学评估显示部分缓解时，HER2拷贝数异常消失。然而，在疾病进展时再次检测到高水平的HER2扩增。最后，在肿瘤进展时鉴定出磷脂酰肌醇-4,5-二磷酸3-激酶催化亚基α突变，这可能解释了对拉帕替尼的获得性耐药。
这是首例HER2阳性RAS/BRAF野生型转移性CRC患者对拉帕替尼单药治疗有反应的病例报告。它强调ctDNA检测是评估抗HER2治疗疗效的一种有效且可行的方法。
