Clinical relevance of circulating tumor DNA in HER2-positive advanced gastric cancer: a collaborative study of a phase Ib trial of dual HER2 and PD-1 targeted therapy (Ni-High).
[BACKGROUND] The combination of anti-programmed cell death-1 antibody with human epidermal growth factor receptor 2 (HER2)-targeted therapy and chemotherapy is widely used in the United States and Eur
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APA
Osumi H, Wakatsuki T, et al. (2025). Clinical relevance of circulating tumor DNA in HER2-positive advanced gastric cancer: a collaborative study of a phase Ib trial of dual HER2 and PD-1 targeted therapy (Ni-High).. Therapeutic advances in medical oncology, 17, 17588359251367344. https://doi.org/10.1177/17588359251367344
MLA
Osumi H, et al.. "Clinical relevance of circulating tumor DNA in HER2-positive advanced gastric cancer: a collaborative study of a phase Ib trial of dual HER2 and PD-1 targeted therapy (Ni-High).." Therapeutic advances in medical oncology, vol. 17, 2025, pp. 17588359251367344.
PMID
40948910
Abstract
[BACKGROUND] The combination of anti-programmed cell death-1 antibody with human epidermal growth factor receptor 2 (HER2)-targeted therapy and chemotherapy is widely used in the United States and Europe for HER2-positive advanced gastric cancer (AGC). Molecular profiles that predict the efficacy of this dual-target therapy are unclear.
[OBJECTIVES] To explore the clinical utility of circulating tumor DNA (ctDNA) as a predictive marker of the efficacy of standard chemotherapy plus HER2 and programmed death-ligand 1 dual-targeted therapy in patients with HER2-positive AGC.
[DESIGN] Collaborative study of the Ni-High phase Ib clinical trial.
[METHODS] A total of 21 patients with tissue-confirmed HER2-positive AGC who received chemotherapy with dual-targeted therapy (capecitabine/S-1, oxaliplatin, trastuzumab, and nivolumab) in a phase Ib clinical trial (UMIN000034222) were enrolled. The association of genomic profiles in plasma ctDNA with tissue HER2 amplification status and their correlation with clinical outcomes was investigated.
[RESULTS] Among the 21 patients studied, 20 (95.2%) showed somatic alterations in ctDNA. amplifications and single-nucleotide variants (SNVs)/indels were found in 12 (57.1%) and 3 (14.3%) patients, respectively. Significant associations between maximum mutant allele frequency (mMAF) and tumor size and between ctDNA and tissue copy numbers were found. Patients without SNV/indels showed longer median progression-free survival (PFS) and overall survival (OS) than those with these alterations. Patients with focal amplification in ctDNA showed better outcomes than those with aneuploidy (median PFS: 20.8 vs 8.4 months, hazard ratio (HR) = 0.08; median OS: NA vs 14.8 months, HR = 0.077). Lower mMAF at cycle 2 was associated with a better response to chemotherapy with dual-targeted therapy.
[CONCLUSION] genetic status and mMAF changes in ctDNA may, respectively, predict and reflect the efficacy of chemotherapy with dual-targeted therapy in HER2-positive AGC.
[TRIAL REGISTRATION] UMIN000034222.
[OBJECTIVES] To explore the clinical utility of circulating tumor DNA (ctDNA) as a predictive marker of the efficacy of standard chemotherapy plus HER2 and programmed death-ligand 1 dual-targeted therapy in patients with HER2-positive AGC.
[DESIGN] Collaborative study of the Ni-High phase Ib clinical trial.
[METHODS] A total of 21 patients with tissue-confirmed HER2-positive AGC who received chemotherapy with dual-targeted therapy (capecitabine/S-1, oxaliplatin, trastuzumab, and nivolumab) in a phase Ib clinical trial (UMIN000034222) were enrolled. The association of genomic profiles in plasma ctDNA with tissue HER2 amplification status and their correlation with clinical outcomes was investigated.
[RESULTS] Among the 21 patients studied, 20 (95.2%) showed somatic alterations in ctDNA. amplifications and single-nucleotide variants (SNVs)/indels were found in 12 (57.1%) and 3 (14.3%) patients, respectively. Significant associations between maximum mutant allele frequency (mMAF) and tumor size and between ctDNA and tissue copy numbers were found. Patients without SNV/indels showed longer median progression-free survival (PFS) and overall survival (OS) than those with these alterations. Patients with focal amplification in ctDNA showed better outcomes than those with aneuploidy (median PFS: 20.8 vs 8.4 months, hazard ratio (HR) = 0.08; median OS: NA vs 14.8 months, HR = 0.077). Lower mMAF at cycle 2 was associated with a better response to chemotherapy with dual-targeted therapy.
[CONCLUSION] genetic status and mMAF changes in ctDNA may, respectively, predict and reflect the efficacy of chemotherapy with dual-targeted therapy in HER2-positive AGC.
[TRIAL REGISTRATION] UMIN000034222.