BACKGROUND 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 ...BACKGROUND 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.CASE SUMMARY 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.CONCLUSION 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.展开更多
文摘BACKGROUND 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.CASE SUMMARY 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.CONCLUSION 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.
