Evaluation of a trastuzumab-containing treatment regimen for patients with unresectable advanced or recurrent gastric cancer

Abstract

Abstract. The present study aimed to evaluate the efficacy and safety of trastuzumab plus chemotherapy for patients with unresectable advanced or recurrent gastric cancer. A retrospective analysis of 213 patients with unresectable advanced or recurrent gastric cancer who received systemic chemotherapy, including 15 patients who were also administered trastuzumab, at Kochi Medical School between 2007 and 2013 was performed. The overall survival was compared between patients who received trastuzumab plus chemotherapy and patients who received chemotherapy alone, and the safety and efficacy of the trastuzumab-containing regimen was evaluated. Human epidermal growth factor receptor (HER)2 status was examined in 86 patients, of whom 15 (17.4%) exhibited strong positive HER2 expression. The rate of strong positive HER2 expression was significantly higher for intestinal type tumors compared with diffuse type tumors [23.6 (13/55) vs. 6.5% (2/31); P=0.044]. The median overall survival of the patients treated with trastuzumab was significantly longer compared with that for patients who were not treated with trastuzumab (22.9 vs. 11.6 months; P= 0.014). The objective response rate and disease control rate for trastuzumab plus chemotherapy were 46.7 and 86.7%, respectively. Frequently encountered grade 3-4 toxicities included neutropenia (26.7%; 4/15), anemia (13.3%; 2/15) and fatigue (13.3%; 2/15). Trastuzumab plus chemotherapy is effective for patients with HER2-positive advanced or recurrent gastric cancer, and the frequencies of hematological and non-hematological toxicities experienced by patients in the present study indicated that it can be safely administered clinically. IntroductionGastric cancer is the third most commonly diagnosed cancer type worldwide and one of the leading causes of cancer-associated mortality (1). In patients with recurrent, metastatic, or advanced gastric cancer, chemotherapy can prolong survival and improve quality of life compared with the best supportive care.Human epidermal growth factor receptor (HER)2 is a member of a family of receptors that is associated with tumor cell proliferation, apoptosis, adhesion, migration and differentiation. It is overexpressed in 15-20% of patients with primary gastric and gastroesophageal junction cancers (2,3). Trastuzumab, a monoclonal antibody that targets HER2, induces antibody-dependent cellular cytotoxicity and inhibits HER2-mediated signaling by binding to the extracellular domain of HER2 (4). The trastuzumab for gastric cancer (ToGA) trial recently validated the additive effects of trastuzumab for HER2-positive, unresectable advanced or recurrent gastric cancer. This trial revealed a significant increase in the overall survival and progression-free survival when trastuzumab was used in combination with chemotherapy, thus supporting the use of trastuzumab in individualized, biomarker-based treatment (5). Additionally, it has been shown that second-line and later lines of chemotherapy can significantly improve patient outcomes, and that the additive...

Clinical Implications of Molecular Heterogeneity of Gastric Cancer

“…Interestingly, HER2 overexpression levels were similar in patients from Europe and Asia, whereas they were lower in patients from Central/South America. Overexpression or amplification of HER2 was more common in intestinal GCs than diffuse or mixed types of GC, which was in concordance with other studies [45,46]. In addition, GEJ tumors showed higher rate of HER2 overexpression or amplification than stomach tumors, indicating that GEJ adenocarcinoma differs in etiology and pathogenesis from distal stomach tumors.…”

“…These findings pointed out clinically important aspect, which could underlie the discrepancy between studies and clinical trials, evaluating the benefit of anti-HER2 targeted chemotherapies. First, HER2 expression patterns differ between GC and breast cancer and furthermore, in GC the expression patterns are frequently heterogeneous [44,46,86,88]. The optimal cutoff for selecting patients with GC who would benefit from addition of lapatinib to chemotherapy should be evaluated in further studies; however, at present, the results indicated that the cutoff value, based on FISH assays, could be the ratios 5.01-10.0 and >10.0 [86].…”

Role of ARPC2 in Human Gastric Cancer

“…Trastuzumab, a monoclonal antibody that targets HER2, is one of a mere few targeted therapies that have been used in human gastric cancer [17, 18]. Trastuzumab could partly prolong survival and improve the quality of life of gastric cancer patients.…”

Role of general practice doctor in the treatment of Signet ring cell carcinoma

“…Zračenje takođe ima ograničeni učinak. Biološka terapija se testira u lečenju karcinoma želuca, cetuksimab, ramucirumab, trastuzumab i fosfolipaza D1 antitela obećavaju u rezultatima lečenja HER2 pozitivnih pacijenata sa karcinomom želuca [18,19,20].…”