Phase II study of trastuzumab and cisplatin as first-line therapy in patients with HER2-positive advanced gastric or gastroesophageal junction cancer

Grávalos, Cristina; Gómez‐Martín, Carlos; Rivera, Fernando; Alés, Inmaculada; Queralt, Bernardo; Márquez, Antonia; Jiménez, Ulpiano; Alonso, Vicente; García‐Carbonero, Rocío; Sastre, Javier; Colomer, Ramón; Cortés, Javier; Jimeno, Antonio

doi:10.1007/s12094-011-0637-6

Cited by 74 publications

(53 citation statements)

References 19 publications

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“…The safety profile of trastuzumab in combination with chemotherapy was identical to chemotherapy alone in a study from Spain. No grade IV events were observed confirming the favorable toxicity profile [8]. Trastuzumab is now established as new standard option for the treatment of HER-2-positive advanced gastric or gastro-esophageal junction cancer in combination with chemotherapy.…”

Section: Treatmentmentioning

confidence: 59%

Gastric Cancer: Clinical Aspects, Epidemiology and Molecular Background

et al. 2011

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In 2010, the WHO introduced the seventh edition of the tumor node metastasis (TNM) classification that provides a more detailed classification for both local tumor invasion (T) and lymph node involvement (N) compared with the previous version. The T and N categories of tumors located in the stomach have been further modified with the intention to ensure a better correlation to the prognostic outcome. For the classification of a pN0, the number of lymph nodes has been adjusted to 16.The description of tumors with origin in the esophagus has been simplified and includes tumors of the esophagogastric junction as well as gastric tumors extending to the proximal 5 cm of the stomach. Major changes are further the subclassification of the categories T1 and T4 and the new N categorization now considering the number of lymph nodes involved within tree categories. Furthermore, positive lymph nodes in the region of the celiac trunc are considered as regional in case of esophageal cancers.The validity of the new classification system in its prognostic efficacy was compared to the previous edition. A study conducted in China proved a better prognostic stratification for the new actualized version [1]. Another study from Korea showed similar results for the new TNM system, proving a more detailed prognostic assessment, especially between T2 and T3 and N1 and N2 tumors [2]. The advantage of the new (7th) edition was mainly confirmed for the prognostic value of accurate lymph node assessment [3].Concerning the classification of early gastric cancer (GC) in the new system, a study from Italy confirmed the usefulness of the new classification for metastatic lymph nodes as a prognostic tool in case of early GC. AbstractThe validity and usefulness of the 7th edition of the UICC tumor node metastasis classification in the context of clinical management of gastric cancer are discussed. The most relevant new agent in gastric cancer therapy is trastuzumab for HER2-positive gastric carcinomas. This marks the success of continuous effort of translational research. Trastuzumab, initially applied in palliative settings, is currently being evaluated also in neoadjuvant treatment regimens. Several new meta-analyses support the carcinogenic effect of high salt intake and smoking in the context of Helicobacter pylori infection. Further data have become available on the efficacy of protective agents, acetyl salicylic acid ⁄ nonsteroidal anti-inflammatory drugs, and antioxidants. In search for a successful prevention strategy, the focus is on the identification of individuals at high risk who demand screening (testing) and surveillance. Serological assessment of gastric mucosal abnormalities with increased risk for gastric cancer development is extensively studied, and new data are presented from Asia as well as from Europe. New high-throughput techniques combined with bioinformatic vector analysis open the gate to the identification of new potential diagnostic and therapeutic targets. Furthermore, these approaches allow us to elucidate the int...

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Section: Treatmentmentioning

confidence: 59%

Gastric Cancer: Clinical Aspects, Epidemiology and Molecular Background

et al. 2011

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“…3,6,7). This implies that there is a proportion of the patients who are not responsive to trastuzumab, even though their tumors are conventionally defined as HER2-positive AGC.…”

Section: Introductionmentioning

confidence: 99%

Optimal Patient Selection for Trastuzumab Treatment in HER2-Positive Advanced Gastric Cancer

Ock

Lee

Kim

et al. 2015

Clinical Cancer Research

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Purpose: Chemotherapy plus trastuzumab is standard of care for HER2-positive advanced gastric cancer (AGC). However, not all patients with HER2-positive AGC seem to benefit from trastuzumab. We evaluated the association between treatment outcomes with trastuzumab and HER2 status in patients with HER2-positive AGC.Experimental Design: We enrolled 126 patients with HER2-positive AGC treated with trastuzumab plus chemotherapy in a training cohort. HER2 IHC (N ¼ 126), HER2/CEP17 ratio (N ¼ 66), and HER2 gene copy number (GCN; N ¼ 59) were analyzed, and the optimal values for discriminating overall survival (OS) were determined using receiver operating characteristic (ROC) curve analysis. We validated the findings from the training cohort using an independent validation cohort (N ¼ 72).Results: Patients with HER2 IHC 3þ showed significantly longer OS (29 vs. 15.3 months; P ¼ 0.025) than patients with IHC2þ. An HER2/CEP17 ratio of 4.48 was the optimal cutoff for predicting longer OS (26.9 vs. 14.7 months; P ¼ 0.027). In subgroup analysis, treatment outcomes of patients with IHC 3þ were not influenced by the level of HER2 gene amplification. However, in patients with IHC 2þ, an HER2/ CEP17 ratio more than 3.69 and HER2 GCN more than 7.75 were positive predictive factors for better outcomes with trastuzumab-based chemotherapy. These findings were confirmed in both the validation cohort and the combined cohort.Conclusions: HER2 IHC status, HER2/CEP17 ratio, and HER2 GCN were correlated with clinical outcomes of trastuzumabbased treatment in HER2-positive AGC. Clinical outcomes of patients with IHC 2þ were strongly dependent on the HER2/CEP17 ratio and HER2 GCN.

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“…In addition, Lapatinib demonstrated clinical activity and was well tolerated as first-line monotherapy in HER2-amplified, locally advanced or metastatic breast cancer [25,26]. Recently, laptinib showed a synergistic effect with trastuzumab in vitro and in vivo to inhibit HER2 amplified human gastric cancer cells and animal model [23].…”

Section: Introduction Egfr and Her2 Family With Signal Pathway And Camentioning

confidence: 99%

HER2 Amplification or Overexpression in Upper GI Tract and Breast Cancer with Clinical Diagnosis and Treatment

Zhou¹,

Hick²

2013

Oncogene and Cancer - From Bench to Clinic

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Phase II study of trastuzumab and cisplatin as first-line therapy in patients with HER2-positive advanced gastric or gastroesophageal junction cancer

Abstract: Trastuzumab in combination with cisplatin is an active regimen and has a favourable toxicity profile in advanced HER2-positive gastric or gastroesophageal cancers.

Cited by 74 publications

References 19 publications

Gastric Cancer: Clinical Aspects, Epidemiology and Molecular Background

Gastric Cancer: Clinical Aspects, Epidemiology and Molecular Background

Optimal Patient Selection for Trastuzumab Treatment in HER2-Positive Advanced Gastric Cancer

HER2 Amplification or Overexpression in Upper GI Tract and Breast Cancer with Clinical Diagnosis and Treatment

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