Clinical significance of intratumoral HER2 heterogeneity on trastuzumab efficacy using endoscopic biopsy specimens in patients with advanced HER2 positive gastric cancer

AbstractBackgroundWe recently reported the clinical significance of intratumoral HER2 heterogeneity on trastuzumab efficacy using surgical specimens; patients with homogeneously HER2 positive gastric cancer benefitted more from trastuzumab. However, the majority of patients are diagnosed by endoscopic biopsy, and surgical specimens are not available in these patients. The aim of this study is to verify clinical significance of HER2 heterogeneity on trastuzumab efficacy using biopsy specimens.MethodsEighty-seven patients, who received trastuzumab-based chemotherapy and whose endoscopic biopsy specimens were available for HER2 assessment, were consecutively enrolled. When all tumor cells in all biopsy specimens overexpressed HER2 protein, it was defined as homogeneously HER2 (homo-HER2) positive group, and the others were defined as heterogeneously HER2 (hetero-HER2) positive group. Progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) were evaluated.ResultsThirty-four patients (39%) were diagnosed as the homo-HER2 group and 53 patients (61%) were the hetero-HER2 group. After the median follow-up period of 17.8  months, the median PFS and OS were 7.6 and 17.8 months, respectively. Significant survival differences were shown between the two groups; the homo-HER2 group showed significantly longer PFS (10.8 vs. 6.1 months, HR 0.469 95% CI 0.29–0.77,p = 0.003) and OS (29.3 vs. 14.4 months, HR 0.352 95% CI 0....
Source: Gastric Cancer - Category: Gastroenterology Source Type: research

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Source: Journal of Gastrointestinal Cancer - Category: Cancer & Oncology Source Type: research
ConclusionsPertuzumab exposure in JACOB was consistent with prior studies in advanced gastric cancer and breast cancer. The 840  mg q3w dose allowed the majority of patients in JACOB to achieve target pertuzumab concentrations and appears to be an appropriate dose selection.
Source: Cancer Chemotherapy and Pharmacology - Category: Cancer & Oncology Source Type: research
Purpose of review This manuscript aims at providing an update and overview on the role of Human epidermal growth factor receptor 2 (HER2) testing and HER2-directed therapies in digestive tumors. Recent findings Phase 3 trial data demonstrating a survival benefit of HER2-targeting treatments are limited to gastric cancer. However, HER2 positivity is also found in 5–6% of colorectal, 7% of pancreatic, and 16% of extrahepatic biliary cancers. Although phase 2 trial data support the use of the combination of trastuzumab and lapatinib with chemotherapy in HER2-positive colorectal cancer, the patient's benefit from ta...
Source: Current Opinion in Oncology - Category: Cancer & Oncology Tags: GASTROINTESTINAL TRACT: Edited by Alain Hendlisz Source Type: research
10 –20% of patients with gastric cancer (GC) have HER2+ tumors. Addition of trastuzumab (T) to cisplatin/fluoropyrimidine-based chemotherapy (CT) improved survival in metastatic, HER2+ GC. When pertuzumab (P) w...
Source: BMC Cancer - Category: Cancer & Oncology Authors: Tags: Study protocol Source Type: research
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Source: Gastric Cancer - Category: Gastroenterology Source Type: research
ConclusionsXELOX-trastuzumab is a promising and effective therapy as first-line treatment for patients with HER2-positive AGC, with comparable results to the ones obtained with other “platinum-based” regimens. This scheme is feasible and tolerable with a low incidence of cardiac toxicity.
Source: Cancer Chemotherapy and Pharmacology - Category: Cancer & Oncology Source Type: research
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Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusions: This meta-analysis demonstrated that CD44 overexpression might be an unfavorable prognostic factor for CRC patients and could be used to predict poor differentiation, lymph node metastasis and distant metastasis. Introduction Although therapies for colorectal cancer (CRC) has improved in recent years, colorectal cancer is still the third most common cause of cancer related death worldwide (1). Metastasis are observed in 25% of patients at initial diagnosis and approximately 50% of patients will develop metastasis (2). Presently, the outcome prediction and the therapy schedule determination of CRC patie...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In conclusion, e-As4S4 holds great potential for an alternative therapeutics in the treatment of breast cancer, due to its unique function of correcting the aggressive microenvironment. Introduction Metastasis is the leading cause of breast cancer mortality, which has been one major challenge in clinical treatment (1). In particular, triple-negative breast cancer (TNBC) is characterized by the absence of estrogen receptors (ER), progesterone receptors (PR) and HER2 receptors, which is one of the most aggressive types of breast cancers, marked by high rates of relapse, visceral metastases and early death (2, 3). The...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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Source: Journal of Gastrointestinal Cancer - Category: Cancer & Oncology Source Type: research
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