Stage IV Gastric Cancer HER2-positive for Peritoneal Foci but Negative for Primary Disease Treated by Curative Operation Following Combination Chemotherapy with Trastuzumab

Abstract Background Since the ToGA trial, trastuzumab-based chemotherapy is the standard treatment for HER2 positive stage IV gastric cancer. However, it is not yet clear whether surgical resection after trastuzumab-based chemotherapy (conversion surgery) can improve survival of HER2 positive stage IV gastric cancer. The purpose of this study is to evaluate the prognostic benefit of conversion surgery in HER2 positive stage IV gastric cancer patients. Case presentation We retrospectively investigated the medical records of the patients with HER2 positive (IHC3(+) or IHC2(+)/FISH(+)) stage IV gastric cancer treated with trastuzumab-based chemotherapy as the first line treatment. Overall survival (OS) was compared between patients with conversion surgery and without. Eleven HER2 positive stage IV gastric cancer patients treated with trastuzumab-based chemotherapy as the first line treatment were evaluated. Response rate was 63.6%, and 6 of 11 patients could receive conversion surgery. R0 resection was achieved in four patients. In Kaplan–Meier analysis, patients who received conversion surgery showed significantly better OS than those without surgery (3-year survival rate, 66.7% vs. 20%, P = 0.03). The median OS of patients who achieved R0 resection is 51.8 months. Conclusions Conversion surgery might have a survival benefit for HER2 positive stage IV gastric cancer patients. If curative surgery is technically possible, conversion surgery could be a treatment option for HER2 positive stage IV gastric cancer.

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Can trastuzumab enhance the effectiveness of chemotherapy in patients with resected, HER2-positive, stage II/III, or stage IV gastric cancer?

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.15_suppl.e14501 ◽

2011 ◽

Vol 29 (15_suppl) ◽

pp. e14501-e14501

Author(s):

T. Oshima ◽

C. Kunisaki ◽

S. Fujii ◽

Y. Rino ◽

M. Masuda ◽

...

Keyword(s):

Gastric Cancer ◽

Stage Iv ◽

Stage Ii ◽

Her2 Positive ◽

Stage Iv Gastric Cancer

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Conversion Surgery for Patients With Stage IV HER2-Positive Gastric Cancer: A Report of 3 Patients

International Surgery ◽

10.9738/intsurg-d-16-00184.1 ◽

2017 ◽

Vol 102 (3-4) ◽

pp. 137-140 ◽

Cited By ~ 1

Author(s):

Shin Saito ◽

Yoshinori Hosoya ◽

Hirofumi Fujii ◽

Hideyuki Ohzawa ◽

Akira Tanaka ◽

...

Keyword(s):

Gastric Cancer ◽

Targeted Therapy ◽

Advanced Gastric Cancer ◽

Molecular Targeted Therapy ◽

Stage Iv ◽

Complete Response ◽

Conversion Surgery ◽

Her2 Positive ◽

Stage Iv Gastric Cancer ◽

Metastatic Lesions

Gastric cancer is a common malignancy and remains potentially lethal. The prognosis of patients with stage IV gastric cancer is thought to be poor, but new molecular targeted therapy may benefit patients with advanced gastric cancer. Currently, conversion surgery after chemotherapy with a trastuzumab-containing regimen is reported to be effective in these patients. We present 3 patients with human epidermal growth factor receptor 2 (HER2)–positive advanced gastric cancer who underwent conversion surgery after receiving a trastuzumab-containing chemotherapy regimen. Interestingly, the primary lesion acquired resistance to the trastuzumab-containing regimen, although the metastatic lesions maintained a complete response. The reason why the primary lesions became resistant to trastuzumab remains unclear. More studies are needed to clarify the mechanism of resistance. Conversion surgery, made possible by the use of molecular-targeted therapy, may improve the prognosis of patients with stage IV gastric cancer, particularly if metastatic lesions show a complete response to therapy.

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Abstract 1799: Can trastuzumab enhance the effectiveness of chemotherapy in patients with resected, HER2-positive, Stage II/III or Stage IV gastric cancer

10.1158/1538-7445.am2011-1799 ◽

2011 ◽

Author(s):

Takashi Oshima ◽

Chikara Kunisaki ◽

Shoichi Fujii ◽

Roppei Yamada ◽

Yasushi Rino ◽

...

Keyword(s):

Gastric Cancer ◽

Stage Iv ◽

Stage Ii ◽

Her2 Positive ◽

Stage Iv Gastric Cancer

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Results of the use of trastuzumab combined with different chemotherapy regimens in first-line treatment of HER2-positive disseminated gastric cancer

Medical Council ◽

10.21518/2079-701x-2019-10-120-127 ◽

2019 ◽

pp. 120-127

Author(s):

N. S. Besova ◽

T. A. Titova ◽

S. G. Bagrova ◽

E. S. Obarevich ◽

V. A. Gorbunova ◽

...

Keyword(s):

Gastric Cancer ◽

Objective Response ◽

Stage Iv ◽

Tumour Regression ◽

First Line ◽

Her2 Positive ◽

Mortality Pattern ◽

Stage Iv Gastric Cancer ◽

Triplet Chemotherapy ◽

Doublet Chemotherapy

Gastric cancer (GC) is one of the most common types of malignant tumour worldwide and is ranked fifth in the cancer incidence pattern and third in the cancer mortality pattern. In the Russian Federation, 39.9% of patients are diagnosed with stage IV gastric cancer, 46.6% of patients die within the first year after diagnosis. The combinations of trastuzumab with platinum derivatives and fluoropyrimidines (trastuzumab + doublet) are regarded as the standard therapy against HER2 positive disseminated gastric cancer. We studied the efficacy and toxicity of the combination of trastuzumab with three-component (triple) chemotherapy regimens (docetaxel or irinotecan + platinum derivatives and fluoropyrimidines). In combination of trastuzumab with triplet chemotherapy, an objective response was achieved in 76.7% of cases, with doublet chemotherapy it was achieved in 60% (p = 0.228), of which complete tumour regression was observed in 10%, control of the disease was reported in 96.7% and 95.0 % (p = 1.0) patients, respectively. The median progression-free survival in patients, who received trastuzumab in combination with triplet chemotherapy, was 9.66 months, in combination with doublet chemotherapy was 11.07 months, the difference was not statistically significant (p = 0.800; OR = 0.908; 95% CI: 0.430–1.918). Median survival of patients is not achieved. The obtained results showed that adding a third cytostatic agent to the standard duplet chemotherapy in combination with trastuzumab does not lead to improvement in the treatment outcomes of first-line therapy in patients with HER2-positive disseminated gastric cancer.

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Recent Strategies for Treating Stage IV Gastric Cancer: Roles of Palliative Gastrectomy, Chemotherapy, and Radiotherapy

Journal of Gastrointestinal and Liver Diseases ◽

10.15403/jgld.2014.1121.251.rv2 ◽

2016 ◽

Vol 25 (1) ◽

pp. 87-94 ◽

Cited By ~ 31

Author(s):

Kunihiko Izuishi ◽

Hirohito Mori

Keyword(s):

Gastric Cancer ◽

Performance Status ◽

Locally Advanced ◽

Growth Factor Receptor ◽

Stage Iv ◽

Stage Iv Gastric Cancer ◽

Palliative Gastrectomy ◽

Advanced Tumor ◽

Esophagogastric Cancer ◽

Previously Treated

Recently, many strategies have been reported for the effective treatment of gastric cancer. However, the strategy for treating stage IV gastric cancer remains controversial. Conducting a prospective phase III study in stage IV cancer patients is difficult because of heterogeneous performance status, age, and degree of cancer metastasis or extension. Due to poor prognosis, the variance in physical status, and severe symptoms, it is important to determine the optimal strategy for treating each individual stage IV patient. In the past decade, many reports have addressed topics related to stage IV gastric cancer: the 7th Union for International Cancer Control (UICC) TNM staging system has altered its stage IV classification; new chemotherapy regimens have been developed through the randomized ECF for advanced and locally advanced esophagogastric cancer (REAL)-II, S-1 plus cisplatin versus S-1 in RCT in the treatment for stomach cancer (SPIRITS), trastuzumab for gastric cancer (ToGA), ramucirumab monotherapy for previously-treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD), and ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously-treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW) trials; and the survival efficacy of palliative gastrectomy has been denied by the reductive gastrectomy for advanced tumor in three Asian countries (REGATTA) trial. Current strategies for treating stage IV patients can be roughly divided into the following five categories: palliative gastrectomy, chemotherapy, radiotherapy, gastric stent, or bypass. In this article, we review recent publications and guidelines along with above categories in the light of individual symptoms and prognosis. Abbreviations: APC: argon plasma coagulation; AVAGAST: anti-angiogenic antibody bevacizumab, the avastin in gastric cancer; BSC: best supportive care; CF: cisplatin and fluorouracil; CRP: C-reactive protein; DCF: docetaxel, cisplatin, and 5-FU; FISH: fluorescent in-situ hybridization; GJ: gastrojejunostomy; GPS: Glasgow Prognostic Score; HER: human epidermal growth factor receptor; HR: hazard ratio; NLR: neutrophil-to-lymphocyte ratio; OS: overall survival; PS: performance status; QOL: quality of life; RAINBOW: ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously-treated advanced gastric or gastro-oesophageal junction adenocarcinoma; RCTs: randomized controlled trials; REAL: randomized ECF for advanced and locally advanced esophagogastric cancer; REGARD: ramucirumab monotherapy for previously-treated advanced gastric or gastro-oesophageal junction adenocarcinoma; REGATTA: reductive gastrectomy for advanced tumor in three Asian countries; SEER: Surveillance Epidemiology and End Results; SEMS: self-expandable metal stents; SPIRITS: S-1 plus cisplatin versus S-1 in RCT in the treatment for stomach cancer; ToGA: trastuzumab for gastric cancer; TTP: time-to-progression; VEGFR: vascular endothelial growth factor receptor.

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