Predictive factors of trastuzumab-based chemotherapy in HER2 positive advanced gastric cancer: a single-center prospective observational study

Li, Q.; Li, H.; Jiang, Huiqin; Feng, Yang; Cui, Yuehong; Wang, Y.; Ji, Yuan; Yu, Yiyi; Li, W.; Xu, Chen; Yu, Shaoning; Zhuang, Rongyuan; Liu, T.

doi:10.1007/s12094-017-1772-5

Cited by 22 publications

(31 citation statements)

References 27 publications

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“…To date, gastric cancer (GC) is still one of the most lethal and common cancers worldwide, which is often associated with a high mortality and morbidity (17)(18)(19). The majority of GC patients are diagnosed at an advanced stage and receive a poor prognosis (20).…”

Section: Discussionmentioning

confidence: 99%

NFIB promotes cell growth, aggressiveness, metastasis and EMT of gastric cancer through the Akt/Stat3 signaling pathway

Zhu

Liu

et al. 2018

Oncol Rep

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Nuclear factor I/B (NFIB) plays a crucial role in the progression of several types of cancers. However, its role in gastric cancer (GC) remains unclear. The present study revealed that NFIB was highly expressed in GC tissues and was positively associated with the clinicopathological features of GC patients. Downregulation of NFIB inhibited the tumor growth, migration and aggression of MKN45 and HGC27 cells in vitro. In addition, NFIB expression promoted epithelial‑mesenchymal transition (EMT), which was accompanied with decreased E‑cadherin and increased vimentin expression. Since AKT and Stat3 play an important role in EMT and tumor progression, we examined whether there is a correlation between NFIB and AKT/Stat3 signaling pathways in GC. Our results revealed that NFIB exhibits its oncogenic functions in GC development by regulating the phosphorylation of both AKT and Stat3 molecules. Knocking down the NFIB expression may enhance the phosphorylation of AKT while inhibiting the Stat3 phosphorylation, suggesting that the AKT/Stat3 signaling pathway may be the downstream target of NFIB with which it exerts its roles on GC development. These results revealed that NFIB promotes tumor growth and aggressiveness of GC. In addition, downregulation of NFIB alters the protein kinase B/signal transducers and activators of transcription 3 (AKT/Stat3) axis, which could be a potential molecular mechanism for precise target treatment of GC.

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Section: Discussionmentioning

confidence: 99%

NFIB promotes cell growth, aggressiveness, metastasis and EMT of gastric cancer through the Akt/Stat3 signaling pathway

Zhu

Liu

et al. 2018

Oncol Rep

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“…The patients treated in the phase III studies received trastuzumab plus cisplatin or oxaliplatin plus capecitabine or 5-FU. 6,14,28,32 Seven phase II studies, 23,26,27,[33][34][35][36] five retrospective studies, 19,20,22,25,37 and a prospective observational study 21 were also included. Four phase II studies used S-1, with two in combination with cisplatin 23,35 and two with oxaliplatin.…”

Section: Features Of the Studies Analyzedmentioning

confidence: 99%

“…Safety comparison across the trials analyzed. See also 6,15,17,[19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] AEs, adverse events; SAEs, serious adverse events; TEAEs, treatment-emergent adverse events; Tx, treatment. Considerations by tumor location among studies of trastuzumab plus fluoropyrimidine plus platin Among 12 studies 6,14,[28][29][30][31][32][33][34][35][36][37] in which gastric cancer was the most common, grade !3 AEs ranged from 44% to 84% (Tables 1 and 2).…”

Section: Considerations By Geographical Regionmentioning

confidence: 99%

Safety and efficacy of HER2 blockade by trastuzumab-based chemotherapy-containing combination strategies in HER2+ gastroesophageal adenocarcinoma

et al. 2022

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Since completion of the Trastuzumab for Gastric Cancer study, trastuzumab with doublet chemotherapy (a fluoropyrimidine and a platinum) has been the gold-standard first-line therapy for patients with locally advanced unresectable or metastatic human epidermal growth factor receptor 2-positive (HER2þ) gastroesophageal adenocarcinoma (GEA). The safety and efficacy of 23 studies of first-line trastuzumab plus doublet chemotherapy, without checkpoint inhibitors (n ¼ 19) or with checkpoint inhibitors (n ¼ 4), conducted in patients with locally advanced unresectable or metastatic HER2þ GEA, including phase II/III, prospective, and retrospective observational studies, were summarized. In studies without checkpoint inhibitors, the median duration of trastuzumab treatment ranged from 19.5 to 39.0 weeks and from 15.3 to 30.0 weeks for chemotherapy. In studies with checkpoint inhibitors, the median duration of pembrolizumab/trastuzumab/chemotherapy was 30 weeks, and 18 weeks for chemotherapy. In studies without checkpoint inhibitors, treatment-emergent adverse events (TEAEs) of grade !3 ranged from 32% to 84%. Serious adverse events (SAEs) ranged from 15% to 39%. Adverse events resulting in discontinuation ranged from 0% to 30%. Treatment-related deaths occurred in 0%-9% of patients. In studies with checkpoint inhibitors, TEAEs of grade !3 were 57%. SAEs ranged from 31% to 38%. Adverse events resulting in discontinuation ranged from 5% to 24%. Treatment-related deaths occurred in 0%-3% of patients. In studies without checkpoint inhibitors, objective response rate (ORR) ranged from 39% to 82%, median progression-free survival (PFS) from 5.7 to 11.6 months, and median overall survival (OS) from 11.2 to 27.6 months. In studies with checkpoint inhibitors, ORR ranged from 39% to 86%, median PFS from 8.0 to 13.0 months, and median OS from 19.3 to 27.3 months. This review provides a historical benchmark on safety and efficacy of available first-line chemotherapy-based standard of care for patients with locally advanced unresectable or metastatic HER2þ GEA.

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“…Li et al analyzed whether clinicopathological factors were predictive for progression-free survival (PFS) of patients with trastuzumab-based first-line therapy. They found only liver metastasis and poor performance status to be independently associated with worse PFS [ 20 ].…”

Section: Treatment-related Biomarkers—molecular Targeted Therapymentioning

confidence: 99%

Novel Biomarkers of Gastric Adenocarcinoma: Current Research and Future Perspectives

Niclauss

Gütgemann

Dohmen

et al. 2021

Cancers

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Overall survival of gastric cancer remains low, as patients are often diagnosed with advanced stage disease. In this review, we give an overview of current research on biomarkers in gastric cancer and their implementation in treatment strategies. The HER2-targeting trastuzumab is the first molecular targeted agent approved for gastric cancer treatment. Other promising biomarkers for targeted therapies that have shown relevance in clinical trials are VEGF and Claudin 18.2. Expression of MET has been shown to be a negative prognostic factor in gastric cancer. Targeting the PD-1/PD-L1 pathway with immune checkpoint inhibitors has proven efficacy in advanced gastric cancer. Recent technology advances allow the detection of circulating tumor cells that may be used as diagnostic and prognostic indicators and for therapy monitoring in gastric cancer patients. Prognostic molecular subtypes of gastric cancer have been identified using genomic data. In addition, transcriptome profiling has allowed a comprehensive characterization of the immune and stromal microenvironment in gastric cancer and development of novel risk scores. These prognostic and predictive markers highlight the rapidly evolving field of research in gastric cancer, promising improved treatment stratification and identification of molecular targets for individualized treatment in gastric cancer.

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Predictive factors of trastuzumab-based chemotherapy in HER2 positive advanced gastric cancer: a single-center prospective observational study

Cited by 22 publications

References 27 publications

NFIB promotes cell growth, aggressiveness, metastasis and EMT of gastric cancer through the Akt/Stat3 signaling pathway

NFIB promotes cell growth, aggressiveness, metastasis and EMT of gastric cancer through the Akt/Stat3 signaling pathway

Safety and efficacy of HER2 blockade by trastuzumab-based chemotherapy-containing combination strategies in HER2+ gastroesophageal adenocarcinoma

Novel Biomarkers of Gastric Adenocarcinoma: Current Research and Future Perspectives

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