HER2 in gastric adenocarcinoma: where do we stand today?

2021 ◽  
Author(s):  
Khalil El Gharib ◽  
Makram Khoury ◽  
Hampig Raphael Kourie
Keyword(s):  
Gastric Cancer ◽  
Gastric Adenocarcinoma ◽  
Survival Rates ◽  
Metastatic Gastric Cancer ◽  
Systematic Search ◽  
Google Scholar ◽  
Efficacy And Safety ◽  
Pivotal Trial ◽  
Gastric Adenocarcinomas

Aim: HER2 is a proto-oncogene expressed in 10–30% of gastric adenocarcinomas and is an ideal target for inhibition in malignancy with high recurrence and dismal survival rates. Materials & methods: A systematic search was conducted via PubMed, Google Scholar and the  clinicaltrials.gov database to report the results of ongoing and past studies investigating HER2- inhibitors in gastric cancer. Results: Twenty-five studies were included; ToGA trial is the pivotal trial approving the use of trastuzumab in metastatic gastric cancer, followed by more studies investigating other HER2- inhibitors in this setting, as well as in local and locoregional malignancy. Conclusion: Anti-HER2 molecules are proving efficacy and safety in gastric cancer; the evidence is growing and association with other cancer agents is under investigation.

Phase II Trial of 4′-Epi-Doxorubicin in Locally Advanced or Metastatic Gastric Cancer

1988 ◽  
Vol 74 (3) ◽  
pp. 313-315 ◽  
Author(s):  
Eduardo Cazap ◽  
Roberto Estevez ◽  
Mario Bruno ◽  
Daniel Levy ◽  
Carlos Algamiz ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Adenocarcinoma ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Metastatic Gastric Cancer ◽  
Phase Iii ◽  
Future Studies ◽  
Phase Iii Trials

Patients with locally advanced or metastatic gastric adenocarcinoma received an i.v. bolus of 4′-epi-doxorubicin, 75/mg/m2/cycle, every 21 days. Partial responses were observed in 5 of 23 evaluable patients (21.7%). Treatment was generally well tolerated and toxicity was mild. The response rate to epirubicin appears to be very similar to that reported for doxorubicin. Larger doses of epirubicin could be safely used in future studies, and further evaluation of epirubicin in phase III trials is indicated.

scholarly journals Pathologic Complete Response Following Neoadjuvant Therapy for Gastric Adenocarcinoma: A National Cancer Database Analysis on Incidence, Predictors, and Outcomes

2020 ◽  
pp. 000313482097208
Author(s):  
Christof Kaltenmeier ◽  
Alison Althans ◽  
Maria Mascara ◽  
Ibrahim Nassour ◽  
Sidrah Khan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Neoadjuvant Therapy ◽  
Gastric Adenocarcinoma ◽  
Survival Rates ◽  
Pathologic Complete Response ◽  
Tumor Grade ◽  
Complete Response ◽  
Neoadjuvant Chemoradiation ◽  
National Cancer Database ◽  
The Impact

Introduction With advances in multimodal therapy, survival rates in gastric cancer have significantly improved over the last two decades. Neoadjuvant therapy increases the likelihood of achieving negative margins and may even lead to pathologic complete response (pCR). However, the impact of pCR on survival in gastric cancer has been poorly described. We analyzed the rate and predictors of pCR in patients receiving neoadjuvant therapy as well as impact of pCR on survival. Methods We conducted a National Cancer Database (NCDB) analysis (2004-2016) of patients with gastric adenocarcinoma who received neoadjuvant chemotherapy followed by surgical resection. Results The pCR rate was 2.2%. Following adjustment, only neoadjuvant chemoradiation, non-signet histology, and tumor grade remained as significant factors predicting pCR. pCR was a statistically significant predictor of survival. Conclusion In this NCDB study, pCR was a predictor of survival. Though chemoradiation rather than chemotherapy alone was a predictor of pCR, it was not a predictor of survival. Further studies are needed to elucidate the role of radiation in the neoadjuvant setting and to discern the impact of pCR on survival.

scholarly journals Efficacy and Safety of Trifluridine/Tipiracil Treatment in Patients With Metastatic Gastric Cancer Who Had Undergone Gastrectomy

JAMA Oncology ◽  
2020 ◽  
Vol 6 (1) ◽  
pp. e193531 ◽  
Author(s):  
David H. Ilson ◽  
Josep Tabernero ◽  
Aliaksandr Prokharau ◽  
Hendrik-Tobias Arkenau ◽  
Michele Ghidini ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Metastatic Gastric Cancer ◽  
Efficacy And Safety

scholarly journals Limited Sensitivity of Circulating Tumor DNA Detection by Droplet Digital PCR in Non-Metastatic Operable Gastric Cancer Patients

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 396 ◽  
Author(s):  
Luc Cabel ◽  
Charles Decraene ◽  
Ivan Bieche ◽  
Jean-Yves Pierga ◽  
Mostefa Bennamoun ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Adenocarcinoma ◽  
Metastatic Gastric Cancer ◽  
Digital Pcr ◽  
Circulating Tumor Dna ◽  
Allelic Frequency ◽  
Droplet Digital Pcr ◽  
Perioperative Chemotherapy ◽  
Plasma Samples ◽  
Tumor Dna

This study was designed to monitor circulating tumor DNA (ctDNA) levels during perioperative chemotherapy in patients with non-metastatic gastric adenocarcinoma. Plasma samples were prospectively collected in patients undergoing perioperative chemotherapy for non-metastatic gastric adenocarcinoma (excluding T1N0) prior to the initiation of perioperative chemotherapy, before and after surgery (NCT02220556). In each patient, mutations retrieved by targeted next-generation sequencing (NGS) on tumor samples were then tracked in circulating cell-free DNA from 4 mL of plasma by droplet digital PCR. Thirty-two patients with a diagnosis of non-metastatic gastric adenocarcinoma were included. A trackable mutation was identified in the tumor in 20 patients, seven of whom experienced relapse during follow-up. ctDNA was detectable in four patients (N = 4/19, sensitivity: 21%; 95% confidence interval CI = 8.5–43%, no baseline plasma sample was available for one patient), with a median allelic frequency (MAF) of 1.6% (range: 0.8–2.3%). No patient with available plasma samples (N = 0/18) had detectable ctDNA levels before surgery. After surgery, one of the 13 patients with available plasma samples had a detectable ctDNA level with a low allelic frequency (0.7%); this patient experienced a very short-term distant relapse only 3 months after surgery. No ctDNA was detected after surgery in the other four patients with available plasma samples who experienced a later relapse (median = 14.4, range: 9.3–26 months). ctDNA monitoring during preoperative chemotherapy and after surgery does not appear to be a useful tool in clinical practice for non-metastatic gastric cancer to predict the efficacy of chemotherapy and subsequent relapse, essentially due to the poor sensitivity of ctDNA detection.

scholarly journals Efficacy and safety of capecitabine plus cisplatin in Japanese patients with advanced or metastatic gastric cancer: subset analyses of the AVAGAST study and the ToGA study

2012 ◽  
Vol 16 (2) ◽  
pp. 175-182 ◽  
Author(s):  
Kensei Yamaguchi ◽  
Akira Sawaki ◽  
Toshihiko Doi ◽  
Taroh Satoh ◽  
Yasuhide Yamada ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Japanese Patients ◽  
Metastatic Gastric Cancer ◽  
Efficacy And Safety

scholarly journals Overexpression of UDP-Glucose 4-Epimerase Is Associated with Differentiation Grade of Gastric Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-5
Author(s):  
Maria de Fátima Deodato de Souza ◽  
Antônio Felix da Silva Filho ◽  
Amanda Pinheiro de Barros Albuquerque ◽  
Michael Williams Leal Quirino ◽  
Mário Sérgio de Souza Albuquerque ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Adenocarcinoma ◽  
Validation Cohort ◽  
Histological Grade ◽  
Cohort Analysis ◽  
Tissue Expression ◽  
Positive Staining ◽  
Gastric Adenocarcinomas ◽  
Well Differentiated ◽  
Differential Tissue

The UDP-glucose 4-epimerase (GALE) is a glycosyltransferase, which acts on protein and lipid glycosylation in normal and neoplastic cells. This study is aimed at investigating the differential tissue expression of GALE and its possible association with clinical-pathological parameters and the outcome of gastric adenocarcinoma patients. Seventy-one patients were evaluated in relation to GALE expression by immunohistochemistry. Our results showed that 48 (67.6%) patients were GALE positive and 23 (32.4%) negative. Positive staining was present on well-differentiated and moderate-differentiated histological grade of gastric adenocarcinomas (p<0.0001). There was no significant association with outcome parameters (p>0.05). Besides that, our results corroborated with the validation cohort analysis, where the expression of GALE mRNA was also associated with the histological grade (p<0.001). These results suggest a possible use of this enzyme as a biomarker for well and moderately differentiated tumors.

Efficacy and safety of trastuzumab (T-mab) and paclitaxel for T-mab naïve patients with HER2 positive previously treated metastatic gastric cancer (JFMC45-1102).

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 63-63
Author(s):  
Akira Miki ◽  
Kazuhiro Nishikawa ◽  
Hirokazu Noshiro ◽  
Akira Tsuburaya ◽  
Yasunori Nishida ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Metastatic Gastric Cancer ◽  
Phase Iii ◽  
Left Ventricular Ejection ◽  
Line Treatment ◽  
Efficacy And Safety ◽  
Her2 Positive ◽  
Previously Treated

63 Background: The global, randomized, Phase III ToGA study showed that the first-line treatment of trastuzumab (T-mab) combined with capecitabine and cisplatin a survival (OS) benefit for patients (pts) with HER2-positive metastatic gastric cancer (mGC). However, there is no report concerning about the efficacy and safety of T-mab containing second-line treatment for T-mab naïve patients with HER2-positive mGC. Therefore, we planned a phase II study of paclitaxel plus trastuzumab in this setting. Methods: JFMC45-1102 is multicentre Phase II study. Patient (pts) with HER2 positive (IHC3+ or IHC2+/FISH+), histologically confirmed gastric adenocarcinoma, age≥20, received one or more prior chemotherapy but no prior therapy with T-mab, normal left ventricular ejection fraction (LVEF ≥ 50%) were eligible. Pts received paclitaxel (80 mg/m2on days 1, 8, and, 15 q4w) plus T-mab (8 mg/kg for the initial dose, followed by 6 mg/kg q3w) until disease progression, unacceptable toxicity or patient’s refusal. The primary endpoint was overall response rate evaluated according to RECIST ver1.0 (ORR; Threshold and expected ORR would be 15% and 30%), and the secondary endpoints include progression free survival (PFS), time to treatment failure (TTF), overall survival (OS) and safety. A LVEF assessment was repeated every three months. Results: Between November 2011 to March 2012, 45 pts were enrolled. Pts characteristics were: gender (M/F); 36/9, median age; 69, ECOG PS0/1/2; 34/10/1, advanced/recurrence; 25/20, number of prior treatment (1/2): 40/5. At 16 weeks, 43 pts were ORR and disease control rate (CR+PR+SD) were 37.2% (95% CI; 23.0%-53.3%) and 83.7%(95% CI; 69.3%-93.2%), respectively. The LVEF assessment was performed in 31 patients. More than 10% decrease in LVEF was observed in only one patient, although total incidence of decrease in LVEF was 56% (17/31 pts). Conclusions: Combination chemotherapy of paclitaxel plus trastuzumab is generally well tolerated and showed promising activity for T-mab native patients with HER2-positive previously treated advanced or recurrent gastric cancer. Clinical trial information: UMIN000006223.

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