Metabolic landscape of advanced gastric cancer according to HER2 and its prognostic implications

In advanced gastric cancer (AGC), HER2 is a validated therapeutic target. However, the metabolic landscape of AGC based on HER2 status has not been reported. Furthermore, the prognostic value of HER2 in AGC is under debate. The purpose of this study was to determine the metabolic landscape and prognosis on the basis of HER2 status in AGC.

We analyzed 866 AGC patients treated with palliative chemotherapy and whose HER2 status was evaluated. HER2 positivity was defined as HER2 IHC 3+ or HER2/CEP17 ratio ≥2. Among them, 363 patients were evaluated with (18)F FDG-PET before chemotherapy. We analyzed mSUV (maximal standardized uptake value) according to HER2 status and clinical outcomes.

Among 866 patients, 225 (26.0 %) had HER2+ GC. The mSUV of HER2+ GC was significantly higher than that of HER2- GC (12.6 vs. 8.7, p < 0.001). Increased HER2 IHC positivity was correlated with increased mSUV (IHC-: 8.1, IHC 1+: 8.2, 2+: 11.4, 3+: 13.2, p < 0.001). Excluding HER2+ patients who received HER2-targeting agents, OS of patients was not different by HER2 status (12.5 vs. 11.9 months, p = 0.688). However, according to tumor metabolism, patients with higher mSUV showed worse OS regardless of HER2 positivity (mSUV < 12.8:14.8, ≥12.8:8.6 months, p < 0.001).

Tumor metabolism of AGC adversely influenced OS under treatment with cytotoxic chemotherapy. Tumor metabolism was higher in HER2+ AGC than HER2-. However, HER2 was not a prognostic factor in patients who received chemotherapy without HER2-targeting agents.