Association between HER2 heterogeneity and clinical outcomes of HER2-positive gastric cancer patients treated with trastuzumab.

Autor: Bang, Kyunghye, Cheon, Jaekyung, Park, Young Soo, Kim, Hyung-Don, Ryu, Min-Hee, Park, Yangsoon, Moon, Meesun, Lee, Hyungeun, Kang, Yoon-Koo
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Zdroj: Gastric Cancer; Jul2022, Vol. 25 Issue 4, p794-803, 10p
Abstrakt: Background: The GASTHER1 study showed that re-evaluation of HER2 status rescued 8% of HER2-positive gastric cancer (GC) patients with initially HER2-negative GC. Since rescued HER2 positivity represents HER2 heterogeneity, we aimed to investigate this in a larger cohort with longer follow-up duration. Methods: Data of 153 HER2-positive advanced GC patients who received first-line trastuzumab-based chemotherapy were analyzed. Repeat endoscopic biopsy was performed in patients with initially HER2-negative GC. Survival outcomes were analyzed according to the immunohistochemistry (IHC) score (IHC 2+ /in situ hybridization [ISH] + vs IHC 3+), HER2 status (initially vs rescued HER2 positive), and H-score. Results: IHC 2+ /ISH + patients showed worse progression-free survival (PFS) and overall survival (OS) than those with IHC 3+ (p < 0.05). Rescued HER2-positive patients showed worse PFS and OS than initially HER2-positive patients (p < 0.05). Although survival outcomes were comparable according to HER2 status in IHC 2+ /ISH + patients, initially HER2-positive patients showed more favorable PFS and OS than rescued HER2-positive patients (p < 0.05) among those with IHC 3+. Among the subgroups determined by HER2 status and IHC score, the initially IHC 3+ subgroup had the highest H-score. The low H-score group (H-score ≤ 210) had significantly worse survival outcomes than the high H-score group (H-score > 210) (p < 0.05). An H-score of ≤ 210 was independently associated with shorter OS (HR = 1.54, 95% CI 1.02–2.31, p = 0.04). Conclusions: Rescued HER2-positive patients showed worse clinical outcomes than initially HER2-positive patients, especially those with IHC 3+. This finding highlights the impact of HER2 heterogeneity, which can be quantified indirectly as an H-score. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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