Depth of response predicts the clinical outcome of advanced HER2-positive gastric cancer to trastuzumab-based first-line chemotherapy

Accumulating evidence suggests that response-related parameters such as depth of response (DpR) might be associated with survival in colorectal cancer, which has not been shown in gastric cancer. This study aimed to evaluate whether DpR was associated with clinical outcomes in HER2-positive AGC patients treated with trastuzumab-based chemotherapy. Fifty-seven HER2-positive AGC patients who were treated with trastuzumab in combination with fluoropyrimidines plus cisplatin therapy as first-line treatment were retrospectively enrolled. DpR was defined as the percent maximal tumor shrinkage of target lesions observed at the lowest point compared with baseline. The cutoff DpR level to discriminate better survival was based on receiver-operating characteristic curve analysis. Association of DpR with progression-free survival (PFS) and overall survival (OS) was assessed using the multivariable Cox proportional hazards model. Median DpR level was 56.8% (range -37.9 to 100%). In multivariate models adjusted for relevant variables, DpR, as a dichotomized variable with a cutoff level of 50% and a continuous variable, was significantly associated with PFS (hazard ratio [HR] 0.39 and 0.97; 95% confidence interval [CI] 0.22-0.68 and 0.96-0.98) and OS (HR 0.38 and 0.98; 95% CI 0.21-0.70 and 0.97-0.99). Clinically meaningful differences in PFS (median, 9.8 vs. 4.1 months; p < 0.001) and OS (median, 24.7 vs. 12.8 months; p < 0.001) were observed between the high DpR (>= 50%) and the low DpR groups (< 50%). Higher DpR predicted favorable outcomes following trastuzumab-based chemotherapy in HER2-positive AGC patients.