scholarly journals REAL-LIFE CLINICAL UTILITY OF RAMUCIRUMAB FOR THE TREATMENT OF PATIENTS WITH DISSEMINATED GASTRIC ADENOCARCINOMA: PRELIMINARY REVIEW OF THE EXPERIENCE OF BLOKHIN RUSSIAN CANCER RESEARCH CENTRE

2017 ◽  
pp. 30-38 ◽  
Author(s):  
N. S. Besova ◽  
T. A. Titova ◽  
V. A. Gorbunova ◽  
O. O. Gordeeva ◽  
A. A. Tryakin ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Single Agent ◽  
Real Life ◽  
Growth Factor Receptor ◽  
Research Centre ◽  
Combination Group ◽  
Preliminary Review ◽  
National Medical ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
Endothelial Growth Factor

Angiogenesis   has  become  an  important  target  in  the  treatment  of  solid  tumors  and  anti-angiogenic   agents   are a  promising  approach  to  cancer  therapy.  Ramucirumab, an  anti-angiogenic   agent   specifically  targeting  vascular endothelial  growth factor receptor-2  (VEGFR-2). In April 2014, the FDA approved ramucirumab as a single  agent  or in combination with paclitaxel  for treatment of advanced gastric or gastroesophageal junction adenocarcinoma (GC) that has progressed on or after prior fluoropyrimidine – or platinumcontaining chemotherapy based on data of REGARD and RAINBOW trials.We evaluated the progression free (PFS), overall survival (OS) and safety of ramucirumab in patients (pts) with advanced GC in routine clinical practice From June 2016  to 20 Sep 2017  40 pts with advanced GC were treated with ramucirumab in the second line treatment as single  agent (8 pts) or in combination with paclitaxel  (26 pts) in N.N.Blokhin National medical research center of oncology.Median PFS (MPFS) and median OS (MOS) was 1,8  and 7,6 mons for monotherapy group. For combination group MPFS was 5,02  mons, MOS was not reached. Ramucirumab had an acceptable safety profile Our data are similar to the data of REGARD and RAINBOW trials.

scholarly journals Results of the use of ramucirumab in combination with paclitaxel or ramucirumab monotherapy as the second line treatment in patients with disseminated HER2-negative gastric or cardioesophageal junction adenocarcinoma: experience of N.N. Blokhin russian cancer research center of the ministry of health of Russia

2018 ◽  
pp. 34-40
Author(s):  
N. S. Besova ◽  
T. A. Titova ◽  
E. V. Trusilova ◽  
V. A. Gorbunova ◽  
A. A. Tryakin ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Single Agent ◽  
Growth Factor Receptor ◽  
Research Center ◽  
Combination Group ◽  
Line Treatment ◽  
Second Line ◽  
National Medical ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
Endothelial Growth Factor

Background.Working out of the second line chemotherapy of advanced gastric adenocarcinoma is a promising approach to cancer therapy. Ramucirumab, an anti-angiogenic agent specifically targeting vascular endothelial growth factor receptor-2 (VEGFR-2). In April 2014, the FDA approved ramucirumab as a single agent or in combination with paclitaxel for treatment of advanced gastric or gastroesophageal junction adenocarcinoma that has progressed on or after prior fluoropyrimidineor platinum containing chemotherapy based on data of REGARD and RAINBOW trials.Materials and Methods: From June 2016 to 15Jan 201837 pts with advanced GC were treated with ramucirumabin the second line treatment as single agent (11 pts) or in combination with paclitaxel (26 pts) in N.N.Blokhin National medical research center of oncology.Results: edian PFS (MPFS) and median OS (MOS) was 1,8 and 7,6 mons for monotherapy group. For combination group MPFS was 4,0mons, MOS -10,6 mons. Ramucirumab had an acceptable safety profileConclusions:ur data are similar to the data of international randomized trials.

scholarly journals RAMUCIRUMAB THERAPY IN PATIENTS WITH ADVANCED GASTRIC AND GASTROESOPHAGEAL JUNCTION ADENOCARCINOMA: A SYSTEMATIC REVIEW

2017 ◽  
Vol 22 (3) ◽  
pp. 116-121
Author(s):  
V. A Gorbounova ◽  
N. S Besova ◽  
M. B Bychkov ◽  
S. V Orlov ◽  
L. M Kogoniya ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Growth Factor Receptor ◽  
Predictive Biomarkers ◽  
Antiangiogenic Agents ◽  
Gastroesophageal Cancer ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
American Society ◽  
Endothelial Growth Factor

Objective. Gastric cancer is the fifth most common malignancy and the third leading cause of the cancer mortality worldwide. It is most often diagnosed at a locally advanced or metastatic stage. Angiogenesis has become an important target in the treatment of solid tumors, and antiangiogenic agents are a promising approach to cancer therapy. In this review, we summarize the current literature on the treatment of gastric and gastroesophageal cancer with ramucirumab, an antiangiogenic agent specifically targeting vascular endothelial growth factor receptor-2 (VEGFR-2). Material and methods. We conducted a systematic search in May 2016 of PubMed and relevant congress proceedings including the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Cancer Congress. Included studies were aimed to prospectively evaluate the efficacy and safety of ramucirumab in advanced gastric or gastroesophageal cancer. Results. Our search yielded 91 publications including 5 manuscripts and 6 congress abstracts meeting the predefined inclusion criteria. Included studies reported outcomes were related to ramucirumab in gastric cancer, published within the past 5 years. Conclusion. Second-line treatment with ramucirumab, either as monotherapy or in combination with paclitaxel, significantly improves the survival of patients with advanced gastric cancer. Ramucirumab is well tolerated and has an acceptable safety profile. Furthermore, the patient quality of life is maintained with delayed both symptom worsening and deterioration of the functional status. Studies are required to identify potential predictive biomarkers of ramucirumab efficacy.

scholarly journals Evolving Management Strategies for Metastatic Esophageal and Gastroesophageal Junction Adenocarcinoma

2018 ◽  
Vol 14 (2) ◽  
pp. 82
Author(s):  
Satya Das ◽  
Michael K Gibson ◽  
◽  
Keyword(s):  
Growth Factor ◽  
Esophageal Adenocarcinoma ◽  
Checkpoint Inhibitors ◽  
Gastroesophageal Junction ◽  
Management Strategies ◽  
Single Agent ◽  
Growth Factor Receptor ◽  
Biologic Agents ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
Area Of Interest

Metastatic or unresectable esophageal and gastroesophageal junction adenocarcinoma represent a devastating disease with 5-year survival rate of <5%. Although cytotoxic chemotherapy with platinum doublet based regimens is initially effective, patients inevitably progress. Patients often decline rapidly after this initial progression, making later lines of therapy a challenge to successfully administer. There have been multiple efforts to incorporate biologic agents, targeting pathways known to be dysregulated in esophageal adenocarcinoma and gastroesophageal junction adenocarcinoma, into existing chemotherapy backbones. Other than therapeutics targeting human epidermal growth factor receptor-2 (HER2) and vascular endothelial growth factor receptor (VEGFR), other strategies have failed. Given the mixed success of biologic agents, along with the promise of immunotherapy to generate durable and sometimes complete responses, immune-agent based trials are a major area of interest for patients with this disease. Checkpoint inhibitors blocking programmed cell death protein-1 (PD-1) and programmed death-ligand 1 (PD-L1) have demonstrated modest single-agent efficacy in patients with progressive esophageal adenocarcinoma and gastroesophageal junction adenocarcinoma. However, other approaches such as novel checkpoint combinations, vaccine-based approaches and autologous T cells hold more promise to change the trajectory of disease.

ZW25, an anti-HER2 bispecific antibody, plus chemotherapy with/without tislelizumab as first-line treatment for patients with advanced HER2-positive breast cancer or gastric/gastroesophageal junction adenocarcinoma: A phase 1B/2 trial-in-progress.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS3145-TPS3145
Author(s):  
Do-Youn Oh ◽  
Hyun Cheol Chung ◽  
Young Hyuck Im ◽  
Chia Jui Yen ◽  
Yee Chao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Antitumor Activity ◽  
Gastroesophageal Junction ◽  
Single Agent ◽  
Tolerability Profile ◽  
First Line ◽  
Her2 Positive ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
Treatment Naïve ◽  
Phase 1B

TPS3145 Background: ZW25 is a novel HER2-targeted antibody that binds two distinct extracellular domains of HER2, allowing for multiple mechanisms of action, including activation of ADCC and inhibition of ligand-dependent and -independent cellular growth. ZW25 is well tolerated and showed single-agent antitumor activity in patients (pts) with advanced HER2-positive cancers. Previous reports suggested that tislelizumab, an investigational anti-PD-1 antibody engineered to minimize binding of FcgR on macrophages in order to abrogate antibody-dependent phagocytosis, was generally well tolerated and had antitumor activity alone and in combination with chemotherapy in pts with advanced solid tumors. Combining HER2-targeted agents with chemotherapy has resulted in improved survival; the highly immunogenic nature of HER2 tumors has led to the development of therapies combining anti-HER2 therapies with immune checkpoint blockade. Methods: This open-label, two cohort phase 1B/2 study is designed to evaluate ZW25 plus chemotherapy ± tislelizumab as first-line therapy in pts (n≈50) with HER2-positive metastatic breast cancer (mBC; cohort 1) or advanced gastric/gastroesophageal junction adenocarcinoma (GC/GEJC; cohort 2). In cohort 1, pts with HER2-positive (IHC3+ or ISH amplified) mBC must be treatment-naïve for metastatic disease and will receive intravenous (IV) ZW25 30 mg/kg plus docetaxel 75 mg/m2 IV once every 3 weeks (Q3W). In cohort 2, treatment-naïve pts with HER2-positive (IHC3+ or IHC2+ with ISH amplification) advanced GC/GEJC will receive ZW25 30 mg/kg plus tislelizumab 200 mg IV and chemotherapy (CAPOX regimen: capecitabine 1000 mg/m2 twice daily and oxaliplatin 130 mg/m2 IV) Q3W. A safety lead-in phase is designed for the first six pts in cohort 2, followed by dose expansion after a safety monitoring committee review. Primary endpoints are the safety/tolerability profile and objective response rate; secondary endpoints include duration of response, time to response, progression-free survival, disease control rate, and overall survival. Clinical trial information: Registered, NCT number pending will provide as soon as available .

scholarly journals KEYNOTE-859: a Phase III study of pembrolizumab plus chemotherapy in gastric/gastroesophageal junction adenocarcinoma

2021 ◽  
Author(s):  
Josep Tabernero ◽  
Yung-Jue Bang ◽  
Eric Van Cutsem ◽  
Charles S Fuchs ◽  
Yelena Yuriy Janjigian ◽  
...  
Keyword(s):  
Metastatic Cancer ◽  
Gastroesophageal Junction ◽  
Growth Factor Receptor ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Double Blind ◽  
Clinical Trial Registration ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
First Line Treatment

Current guidelines recommend two-drug cytotoxic chemotherapy with a fluoropyrimidine (fluorouracil or capecitabine) and a platinum-based agent (oxaliplatin or cisplatin) as first-line treatment for advanced gastric cancer. Pembrolizumab monotherapy has demonstrated durable antitumor activity in patients with advanced programmed death ligand 1-positive (combined positive score ≥1) gastric/gastroesophageal junction adenocarcinoma. Accumulating evidence indicates that combining pembrolizumab with standard-of-care chemotherapy for the treatment of advanced or metastatic cancer improves clinical outcomes. We describe the rationale for and the design of the randomized, double-blind, placebo-controlled, Phase III KEYNOTE-859 study, which is investigating pembrolizumab in combination with chemotherapy as first-line treatment for patients with human epidermal growth factor receptor 2-negative advanced unresectable or metastatic gastric/gastroesophageal junction adenocarcinoma. The planned sample size is 1542 patients, and the primary end point is overall survival. Clinical trial registration: NCT03675737 (ClinicalTrials.gov)

scholarly journals Case report of the rapid achievement of sustained and long-term remission resulting from the use of ramucirumab plus paclitaxel in the second-line treatment of a patient with disseminated gastric adenocarcinoma

2018 ◽  
pp. 150-153
Author(s):  
T. A. Titova ◽  
N. S. Besova ◽  
V. A. Gorbunova ◽  
Yu. P. Kuvshinov ◽  
A. A. Filatov ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
High Efficiency ◽  
Performance Status ◽  
Gastroesophageal Junction ◽  
Growth Factor Receptor ◽  
Metastatic Gastric Cancer ◽  
Best Supportive Care ◽  
Serious Adverse Events ◽  
Endothelial Growth Factor

Ramucirumab is a monoclonal antibody targeting vascular endothelial growth factor receptor 2. In two randomised clinical trials Ramucirumab either alone or in combination with paclitaxel has been found to be safe and effective for patients with previously treated advanced gastric cancer. One of the serious adverse events associated with ramucirumab is bleeding.We report the case of a 56-year-old man with advanced gastric cancer located at the gastroesophageal junction with liver, pulmonary and multiple lymph node metastases, plevritis was treated with a paclitaxel plus Ramucirumab regimen. We demonstrate a case of a cardioesophageal junction bleeding due to the high efficiency of treatment. He was successfully treated with by applying only hemostatical therapy, but after stop the bleeding chemotherapy was not reintroduced. The partial response was maintained for approximately 10 months. The patient died on 28 November 2017.Chemotherapy with best supportive care for metastatic gastric cancer shown the improvement the performance status, help keep the cancer under control and help relieve symptoms during the time.

Ramucirumab and paclitaxel in patients with gastric cancer and prior trastuzumab: subgroup analysis from RAINBOW study

2019 ◽  
Vol 15 (23) ◽  
pp. 2723-2731 ◽  
Author(s):  
Ferdinando De Vita ◽  
Christophe Borg ◽  
Gabriella Farina ◽  
Ravit Geva ◽  
Iris Carton ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Subgroup Analysis ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Progression Free Survival ◽  
Combination Group ◽  
Clinical Trial Registration ◽  
Trastuzumab Therapy ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
Registration Number

Aim: This subgroup analysis of the RAINBOW study evaluated the efficacy and safety of ramucirumab in patients with gastric cancer/gastroesophageal junction adenocarcinoma who received prior trastuzumab therapy. Patients & methods: Of adult patients enrolled in the RAINBOW study, 39 had received prior trastuzumab therapy. Of these, 20 patients were treated with ramucirumab plus paclitaxel and 19 patients with placebo plus paclitaxel within the RAINBOW trial. Results: Overall survival was longer with ramucirumab plus paclitaxel (11.4 months; 95% CI: 7.0–17.9) versus placebo plus paclitaxel (7.0 months; 95% CI: 3.4–14.6), hazard ratio: 0.68 (0.33–1.41); p = 0.30. Longer progression-free survival, higher objective response were observed in ramucirumab combination group. Conclusion: Ramucirumab plus paclitaxel demonstrated efficacy benefits with manageable safety profile in a subgroup of patients pretreated with trastuzumab.Clinical trial registration number: NCT01170663.

KEYlargo: A phase II study of first-line pembrolizumab (P), capecitabine (C), and oxaliplatin (O) in HER2-negative gastroesophageal (GE) adenocarcinoma.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 228-228
Author(s):  
Hope Elizabeth Uronis ◽  
Christel Rushing ◽  
Gerard C. Blobe ◽  
Shiaowen David Hsu ◽  
Niharika B. Mettu ◽  
...  
Keyword(s):  
Phase Ii ◽  
Gastroesophageal Junction ◽  
Single Agent ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Complete Response ◽  
Clinical Activity ◽  
First Line ◽  
Tumor Biopsy ◽  
Gastroesophageal Junction Adenocarcinoma

228 Background: Gastric and esophageal adenocarcinomas are a leading cause of cancer death worldwide. Many of these patients (pts) present with locally advanced unresectable or metastatic disease and are treated with combination cytotoxic chemotherapy. Single agent P is FDA approved for patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma (GEJ) whose tumors have a combined positive score (CPS) ≥ 1 after disease progression on or after two lines of therapy including fluoropyrimidine and platinum and her2/neu-targeted therapy (if indicated). More effective therapy is needed earlier in the disease trajectory. We conducted a single-arm phase II trial to establish the safety and efficacy of first-line C and O + P. Methods: Pts with previously untreated metastatic GE adenocarcinoma regardless of PDL-1 status received intravenous (IV) P 200mg with IV O 130mg/m2 every three weeks and oral C 850mg/m2 twice daily for 14 days on/7 days off. After the 6 patient safety cohort, pts first completed a biomarker cycle that included fresh tumor biopsy before P and one week after P before chemotherapy started. Archived FFPE tumor samples were also obtained from all pts with available tissue. The primary endpoint was progression free survival (PFS); secondary endpoints included response rate (RR) and overall survival (OS). Results: 36 pts were enrolled and 34 pts were evaluable for efficacy (1 pt withdrew for personal reasons before end of cycle 1 and 1 pt had immune-related toxicity during cycle 1 and was taken off study before any efficacy assessment). 9 pts (26%) had an esophageal primary, 18 pts (53%) had a GEJ primary and 7 pts (21%) had a gastric primary. Median PFS was 7.6 months [95% CI: 5.8 to 12.2], RR was 72.7% [95% CI: 57% to 88%], and median OS was 15.8 months [95% CI: 11.6 to NE]. 27 patients (81.8%) had decrease in disease burden (ranging from -19% to -100%). After > 18 months of follow-up, 5 patients remained in durable complete response (CR). Immune-mediated treatment related adverse events (TRAEs) included thyroid disorders (n=5; 14%), colitis (n=4; 11%), adrenal insufficiency (n=2; 5%), and type 1 diabetes (n=1). Sixteen patients (44%) experienced grade 3 or 4 TRAEs. There were no grade 5 TRAEs. Conclusions: The combination of C and O + P had acceptable safety and significant clinical activity. These promising results indicate that C and O + P merits further study as a first line option for patients with unresectable locally advanced or metastatic GE adenocarcinoma. Updated survival and correlative data will be presented. Clinical trial information: NCT03342937.

HER2/neu Gene Amplification and Protein Overexpression in Gastric and Gastroesophageal Junction Adenocarcinoma: A Review of Histopathology, Diagnostic Testing, and Clinical Implications

2012 ◽  
Vol 136 (6) ◽  
pp. 691-697 ◽  
Author(s):  
Jaclyn F. Hechtman ◽  
Alexandros D. Polydorides
Keyword(s):  
Gastroesophageal Junction ◽  
Diagnostic Testing ◽  
Growth Factor Receptor ◽  
Diagnostic Techniques ◽  
Clinical Implications ◽  
Protein Overexpression ◽  
Her2 Protein ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
Epidermal Growth ◽  
Gastroesophageal Adenocarcinoma

Amplification of the human epidermal growth factor receptor 2/neu (HER2/neu) gene and overexpression of the HER2 protein (HER2) have been shown to occur in gastric and gastroesophageal junction adenocarcinoma in a number of studies. With a dismal survival rate, patients with these cancers stand to benefit from the identification of possible molecular targets such as HER2 for both prognostic and therapeutic purposes. Although these and other carcinomas that overexpress HER2 may have a poorer prognosis and exhibit resistance to conventional chemotherapy, they have also recently been shown to respond to targeted therapy with the anti-HER2 antibody trastuzumab. Here, we briefly review the molecular biology, histopathology, diagnostic techniques, and interpretation, as well as the clinical implications, of HER2 amplification/overexpression in gastric and gastroesophageal adenocarcinoma.

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