Changes in plasma cfDNA ERBB2 copy number reflect prognosis in HER2-positive gastric cancer: a correlative analysis of the KSCC-TROX A2 study.

BACKGROUND

In HER2-positive advanced or recurrent gastric cancer, tissue-based HER2 assessment has been established; however, the clinical relevance of ERBB2 copy number (CN) measured from plasma cell-free DNA (cfDNA), particularly its longitudinal change during treatment, remains unclear.

METHODS

This was a prespecified ancillary correlative analysis of the phase II KSCC-TROX trial (jRCTs071190007; UMIN000036867), evaluating whether changes in cfDNA ERBB2 CN (ΔCN) reflect clinical outcomes. Of the 66 patients included in the TROX trial analysis set, 55 with baseline blood samples comprised Cohort A, and 34 with paired follow-up samples comprised Cohort B. ERBB2 CN was quantified using droplet digital PCR.

RESULTS

Baseline ERBB2 CN was associated with tumor HER2 immunohistochemistry score but not with progression-free survival (PFS) or overall survival (OS) when dichotomized at a cut-off of 2.5. In Cohort B, an increase in ERBB2 CN (ΔCN > 0) was significantly associated with shorter PFS compared with ΔCN ≤ 0 (p = 0.008), which was maintained in multivariable analysis (p = 0.001). OS was also significantly shorter in patients with ΔCN > 0 (p = 0.024).

CONCLUSIONS

An increase in cfDNA ERBB2 CN during treatment was independently associated with shorter PFS in HER2-positive advanced gastric cancer. Assessment of ERBB2 CN change may provide a useful biomarker for treatment monitoring and prognostic stratification.