Correlation between human epidermal growth factor receptor 2 expression level and efficacy of trastuzumab beyond progression in metastatic gastric cancer

Narita,Yukiya; Kadowaki,Shigenori; Masuishi,Toshiki; Taniguchi,Hiroya; Takahari,Daisuke; Ura,Takashi; Ando,Masashi; Tajika,Masahiro; Niwa,Yasumasa; Eto,Tetsuya; Hara,Hiroki; Asayama,Masako; Yamaguchi,Kensei; Yatabe,Yasushi; Muro,Kei

doi:10.3892/ol.2017.6409

Correlation between human epidermal growth factor receptor 2 expression level and efficacy of trastuzumab beyond progression in metastatic gastric cancer

Authors:
- Yukiya Narita
- Shigenori Kadowaki
- Toshiki Masuishi
- Hiroya Taniguchi
- Daisuke Takahari
- Takashi Ura
- Masashi Ando
- Masahiro Tajika
- Yasumasa Niwa
- Tetsuya Eto
- Hiroki Hara
- Masako Asayama
- Kensei Yamaguchi
- Yasushi Yatabe
- Kei Muro
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Affiliations: Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi 464‑8681, Japan, Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya, Aichi 464‑8681, Japan, Department of Gastroenterology, Tsuchiura Kyodo General Hospital, Tsuchiura, Ibaraki 300‑0028, Japan, Department of Gastroenterology, Saitama Cancer Center Hospital, Saitama 362‑0806, Japan, Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Aichi 464‑8681, Japan
Published online on: June 19, 2017 https://doi.org/10.3892/ol.2017.6409
Pages: 2545-2551

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Abstract

There is currently no clinical data regarding the efficacy of trastuzumab treatment for the progression of human epidermal growth factor receptor 2 (HER2)‑positive advanced gastric cancer (AGC) occurring during trastuzumab-based chemotherapy. The aim of this study was to retrospectively examine the clinical benefits of trastuzumab for HER2‑positive AGC patients who progressed during first‑line trastuzumab‑based chemotherapy. Among the 108 patients treated with trastuzumab combined with fluoropyrimidine and cisplatin as first‑line therapy, 46 HER2‑positive AGC patients who received cytotoxic agents with or without trastuzumab subsequent to disease progression were included. Of these, the efficacy and safety outcomes of 26 patients who continued trastuzumab were compared with those of the 20 patients who discontinued trastuzumab. No difference in response rate (18.2 vs. 15.8%, P=1.00) was observed between the two groups. Progression‑free survival (PFS) time was numerically longer in the chemotherapy combination with trastuzumab group than in the chemotherapy combination without trastuzumab group (median, 4.0 vs. 2.3 months), with no significance [hazard ratio (HR), 0.63; P=0.14]. In the subset analysis, continuation of trastuzumab significantly improved PFS time in selected subgroups of patients with tumors exhibiting HER2 expression scores of 3+ (HR, 0.41; P=0.04), intestinal‑type histology (HR, 0.32; P<0.01), and a first PFS time of >6 months (HR, 0.44; P=0.04). The survival times for the trastuzumab beyond progression (TBP) and non‑TBP groups were similar (HR, 1.06; P=0.88), with equivalent overall survival times in the subgroups with immunohistochemistry scores of 3+ (HR, 0.97; P=0.94), intestinal‑type histology (HR, 0.53; P=0.19), and a first PFS time of >6 months (HR, 0.62; P=0.31). There were no differences in the incidence rates of toxicity, including cardiac dysfunction, between the two groups. The study results suggest that selected HER2‑positive AGC patients may benefit from trastuzumab continuation during first progression, and further prospective studies are warranted.

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