Details

Autor(en) / Beteiligte

• Seo, Seyoung
• Ryu, Min-Hee
• Park, Young Soo
• Ahn, Ji Yong
• Park, Yangsoon
• Park, Sook Ryun
• Ryoo, Baek-Yeol
• Lee, Gin Hyug
• Jung, Hwoon-Young
• Kang, Yoon-Koo

Titel

Loss of HER2 positivity after anti-HER2 chemotherapy in HER2-positive gastric cancer patients: results of the GASTric cancer HER2 reassessment study 3 (GASTHER3)

Ist Teil von

• Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2019-05, Vol.22 (3), p.527-535

Ort / Verlag

Singapore: Springer Singapore

Erscheinungsjahr

2019

Quelle

SpringerLink Journals

Beschreibungen/Notizen

• Background Although discordance in HER2 positivity between primary and metastatic lesions is well established, changes in HER2 positivity after anti-HER2 therapy have not been well evaluated in gastric cancer. We aimed to evaluate whether HER2 expression in gastric cancer is affected by trastuzumab therapy. Methods We enrolled 48 HER2-positive advanced gastric cancer patients treated with trastuzumab-containing first-line chemotherapy and had paired biopsies at baseline and after progression. Results At baseline, HER2 was positive, with immunohistochemistry (IHC) 2+ and in situ hybridization (ISH)+ in five patients, and with IHC 3+ in 43 patients. Fourteen patients (29.1%) exhibited loss of HER2 positivity on post-progression biopsy: 10 with IHC 0 or 1+, and four with IHC 2+/ISH−. HER2 remained positive on second biopsy in 34 patients: four with IHC 2+/ISH+, and 30 with IHC 3+. Median H -scores decreased from 225 to 175 ( p  = 0.047). HER2 genetic heterogeneity was defined in one of 34 ISH-assessable patients (2.9%) at baseline and seven of 32 (21.9%) at second biopsy. Among 13 patients who received second-line trastuzumab emtansine, three showed HER2-negative conversion; they had no objective response and short progression-free survival (1.2, 1.3, and 3.4 months). Patients with stable HER2 status had a 44% response rate and median progression-free survival of 2.7 (0.4–36.8) months. Conclusion A substantial portion of HER2-positive patients showed HER2-negative conversion with increased HER2 genetic heterogeneity after failure of trastuzumab-containing chemotherapy. Loss of HER2 positivity could be predictive of second-line anti-HER2 treatment, suggesting a need to reexamine HER2 status before initiating second-line anti-HER2 therapy.