Pharmacokinetic and exposure –response analysis of pertuzumab in patients with HER2-positive metastatic gastric or gastroesophageal junction cancer

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

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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
In this study, we evaluated the therapeutic benefit of combining the TAB004 antibody with Liposomal-MSA-IL-2 in immune competent and human MUC1 transgenic (MUC1.Tg) mouse models of PDA and investigated the associated immune responses. Treatment with TAB004 + Lip-MSA-IL-2 resulted in significantly improved survival and slower tumor growth compared to controls in MUC1.Tg mice bearing an orthotopic PDA.MUC1 tumor. Similarly, in the spontaneous model of PDA that expresses human MUC1, the combination treatment stalled the progression of pancreatic intraepithelial pre-neoplastic (PanIN) lesion to adenocarcinoma. Treatment with t...
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
Conclusions: The newly developed radiomic signature was a powerful predictor of LN metastasis and the radiomics nomogram could facilitate the preoperative individualized prediction of LN status. Introduction Gastric cancer (GC) is one of the most common malignant tumors and the second leading cause of cancer-related deaths worldwide (1). Accurate evaluation of lymph node metastasis (LNM) status in GC patients is vital for prognosis and treatment decisions (2–4). Some histopathologic factors and biomarkers (e.g., lymphatic invasion, matrix metalloproteinase-2) are found to be able to predict LNM in GC, but mos...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Li Liu, Jiajing Lin and Hongying He* Department of Obstetrics and Gynecology, Liuzhou Worker’s Hospital, Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, China Background and Objective: Endometrial cancer (EC) is a common gynecological malignancy worldwide. Despite advances in the development of strategies for treating EC, prognosis of the disease remains unsatisfactory, especially for advanced EC. The aim of this study was to identify novel genes that can be used as potential biomarkers for identifying the prognosis of EC and to construct a novel risk stratification using these genes. Me...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
This study was supported by the Shanghai Sailing Program [grant number 17YF1425200, 2017]; Chinese National Natural Science Funding [grant number 81702249, 2017]; Science and Technology Commission of Shanghai Municipality [grant number 17511103403, 2017]; The funder has no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Conflict of Interest Statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Acknowledgments We acknowledge the ex...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsTrastuzumab PK for the intravenous formulation was well-described across cancer types, disease status, and regimens. No dose adjustment is required for any of the identified patient covariates. A 7-month serum washout period for trastuzumab is recommended. A reloading dose is required if a maintenance dose is missed by>  1 week.
Source: Cancer Chemotherapy and Pharmacology - Category: Cancer & Oncology Source Type: research
ConclusionsDespite optimal management of diarrhea including treatment of grade I symptoms, it was not possible to treat the patients above a dose of 20  mg of afatinib daily in combination with 3-weekly trastuzumab. The MTD of afatinib in combination with the recommended 3-weekly dose of trastuzumab was 20 mg daily.
Source: Cancer Chemotherapy and Pharmacology - Category: Cancer & Oncology Source Type: research
CONCLUSION: Our results provide for the first time a detailed molecular profile of concurrent genetic alterations in HER2-positive AGC. PI3K pathway activation could be used as a predictive marker of worse outcome in this patient population. In addition, gains in copy number of other TKR genes in this subgroup may also influence the survival benefit obtained with trastuzumab. IMPLICATIONS FOR PRACTICE: This article reports, for the first time, a detailed molecular profile of genomic alterations in patients with HER2-positive advanced gastric cancer (AGC). PI3K/Akt/mTOR signaling pathway activation seems to have a diff...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Oncologist Source Type: research
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