A study of the combination of oxaliplatin, capecitabine, and trastuzumab and chemo-radiotherapy in the adjuvant setting in operated patients with HER2+ gastric or gastroesophageal junction cancer (TOXAG study).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 26-26
Author(s):  
Huseyin Abali ◽  
Suayib Yalcin ◽  
Cem Onal ◽  
Faysal Dane ◽  
Berna Oksuzoglu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lymph Node ◽  
Gastroesophageal Junction ◽  
High Rate ◽  
Combination Regimen ◽  
Adjuvant Setting ◽  
Her2 Positive ◽  
Weekly Cycle ◽  
D2 Lymph Node Dissection ◽  
Gastroesophageal Junction Adenocarcinoma

26 Background: We evaluated the safety and tolerability of trastuzumab (T) in combination with oxaliplatin (O), capecitabine (C) and chemo-radiotherapy in the adjuvant setting in operated, HER-2 positive gastric or gastroesophageal junction adenocarcinoma patients. Methods: We have screened 212 and enrolled 34 patients who were curatively resected (R0, R1 with partial or total gastrectomy, with D2 lymph node dissection) and were HER2-positive (IHC 2+/FISH+ or IHC 3+). The primary objectives were safety and tolerability of the treatment combination and secondary objectives were disease-free and overall survival rates. Patients received T 8 mg/kg intravenously (iv) on Day 1 of cycle 1 and 6 mg/kg iv on day 1 of every following 3-weekly cycle for 1 year as 17 cycles, O 100 mg/m2 iv on Day 1 of cycles 1-3 and C 850 mg/m2 orally twice daily on days 1-14 of cycles 1-3 and 5 days per week during chemo-radiotherapy. Radiotherapy was given at a total dose of 45 Gy divided into 25 doses 5 treatment days per week for 5 weeks starting from the 1st day of cycle 4. Results: The median age was 57 years and 73.5% were male, 97.0% had an ECOG PS score ≤ 1,33, 97.0% had D2 lymph node resection. Staging was 3A or higher at the time of diagnosis in 76.4% of patients. Patients had high rate of tolerability to the combination regimen (90.3%) and successfully completed 3 cycles of O+C+T plus chemoradiotherapy followed by continuation with T, achieving the primary goal of the study by showing a better tolerability rate as compared to tolerability reported for INT0116 study (p = 0.0068). After 25 months of follow-up confirmed through a telephone visit, 59.8% patients were still alive and median overall survival was not yet reached. Twelve patients died secondary to disease progression. There were no deaths due to toxicity and 6 dose reductions overall (1 for T, 2 for O and 3 for C). T was stopped in one patient; C was temporarily interrupted 11 times (mostly during radiotherapy) and stopped in 1 patient. Conclusions: T in combination with C, O and radiotherapy in the adjuvant setting for gastric or gastroesophageal junction adenocarcinoma seems safe and tolerable. Clinical trial information: NCT01748773.

Efficacy and safety of camrelizumab combined with FOLFOX as neoadjuvant therapy for patients with resectable locally advanced gastric and gastroesophageal junction adenocarcinoma who received D2 radical gastrectomy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16549-e16549
Author(s):  
Yuzhou Zhao ◽  
Guangsen Han ◽  
Jing Zhuang ◽  
Zhimeng Li ◽  
Gangcheng Wang ◽  
...  
Keyword(s):  
Lymph Node ◽  
Neoadjuvant Therapy ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
R0 Resection ◽  
Lymph Node Yield ◽  
D2 Lymph Node Dissection ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
The Mean

e16549 Background: Neoadjuvant chemotherapy for patients with locally advanced gastric and gastroesophageal junction adenocarcinoma (GC/GEJC) can improve the overall survival without increasing operation risk. Nowadays, immunotherapy has become a new promising neoadjuvant treatment. Therefore, we intended to evaluate the safety and efficacy of camrelizumab (anti-PD-1 antibody) combined with FOLFOX as the neoadjuvant therapy for patients with locally advanced GC/GEJC who received D2 radical gastrectomy. Methods: Patients who were diagnosed as resectable locally advanced GC/GEJC received the neoadjuvant treatment of camrelizumab and FOLFOX every 2 weeks for 4 cycles. Imaging evaluation was performed in 2-4 weeks after neoadjuvant therapy. Patients who had no progression disease (PD) were recruited. Eligible patients underwent gastrectomy with D2 lymph node dissection through laparotomy or laparoscopic surgery. The primary end points were safety and R0 resection rate. Results: From July 24 2019 to January 31 2020, 15 patients were recruited. The mean age was 57 years. A total of 10(67%) were males and 5(33%) were females. According to AJCC 8th, cT3 and cT4 were confirmed in 7(47%) patients and 8(53%) patients, N1 and N2 in 7(47%) patients and 8(53%) patients, respectively. During operation, intraperitoneal metastases were found in 2 patients. Of the 13 surgeries, only 2 were laparoscopic and the others were laparotomy. The surgical procedures included Roux-en-Y (9, 69.2%), Billroth II (1, 7.7%) and jejunum interposition (3, 23.1%). Thirteen patients underwent gastrectomy with D2 lymph node dissection and all of them were confirmed R0 resection by postoperative pathology results. The mean lymph node yield was 44.1±13.2 nodes, positive lymph node yield was 1.8±2.8 nodes. Duration time of surgery was 186.5±45.5 minutes, mean blood loss was 219.2±109 ml during the operation. Mean hospital stays were 13.2±2.4 days. Only 1 patient experienced grade 3 pneumonia. Neither serious intraoperative complications nor immune-related adverse events both prior and post operation were observed. There was no treatment-related death. Conclusions: Camrelizumab combined with FLOFOX as neoadjuvant treatment for patients with locally advanced GC/GEJC showed acceptable toxicity and promising efficacy with low complications and mortality. Clinical trial information: NCT03939962 .

scholarly journals A Phase Ii Study Of The Combination Of Oxaliplatin, Capecitabine, And Trastuzumab And Chemo-radiotherapy In The Adjuvant Setting In Operated Patients With Her2+ Gastric Or Gastroesophageal Junction Cancer (Toxag Study), A Turkish Oncology Group Study

2020 ◽  
Author(s):  
Huseyin Abali ◽  
Suayib Yalcin ◽  
Huseyin Cem Onal ◽  
Faysal Dane ◽  
Berna Oksuzoglu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase Ii ◽  
Gastroesophageal Junction ◽  
Disease Free Survival ◽  
R0 Resection ◽  
Her2 Overexpression ◽  
Her2 Positive ◽  
Open Label ◽  
Gastroesophageal Junction Cancer ◽  
Gastroesophageal Junction Adenocarcinoma

Abstract BackgroundTrastuzumab prolonged the overall survival in patients with advanced gastric cancer with HER2 overexpression in combination with chemotherapy. In this phase II open-label prospective study, the tolerability and safety of trastuzumab with chemotherapy, and chemoradiotherapy for curatively resected patients with HER2 + gastric carcinoma was investigated. MethodsThe patients with HER2-positive gastric, or gastroesophageal junction adenocarcinoma, after gastrectomy plus D2 dissection were included. They received 3 cycles of oxaliplatin (100 mg/m2 IV day 1) plus capecitabine (850 mg/m2 PO days 1-14), trastuzumab (8 mg/kg IV day 1 in cycle 1, 6 mg/kg thereafter) every 21 days, followed by chemoradiotherapy. Trastuzumab was given for 1 year.ResultsOf the 212 patients screened, 35 were eligible, and 34 were treated. The median age was 56 years (Min-max: 35-75), male patients constituted 73.5% (n=25), and 33 (97.1%) had gastric adenocarcinoma. R0 resection was performed in 30 (88.2%). The majority (26, 61.7%) were in stage III disease. Most of the AEs were grade I/II, the most frequent grade III side effects were nausea (3, 8.8%), vomiting (3, 8.8%), diarrhoea (2, 5.9%) and weight loss (N=2, 5.9%). Two patients died during the first 3 cycles of chemotherapy and chemoradiotherapy; 1 secondary to pulmonary thrombo-embolism, and the other due to cerebral ischemia. After excluding 2 with early progression and 1 consent withdrawal, of the remaining 31 patients, 28 (90.3%) were able to complete the chemotherapy and chemoradiotherapy part of the trial. After the 25 months follow up period, 21 patients (61.8%) were alive. Overall survival at 12 and 24 months was 75.0% and 65.7%, while disease-free survival at 12 and 24 months was 65.7% and 55.0%, respectively.ConclusionsTrastuzumab in combination with capecitabine, oxaliplatin and radiotherapy as the adjuvant therapy for gastric or gastroesophageal junction adenocarcinoma was considered safe and tolerable. The frequency of HER2 overexpression in curatively resected patients is comparable to that in patients with metastatic disease.

Postoperative Morbidity in Curative Resection of Gastroesophageal Carcinoma Does Not Impact Long-term Survival

2015 ◽  
Vol 81 (12) ◽  
pp. 1228-1231
Author(s):  
Jennifer E. Samples ◽  
Anna C. Snavely ◽  
Michael O. Meyers
Keyword(s):  
Overall Survival ◽  
Lymph Node ◽  
Neoadjuvant Therapy ◽  
Postoperative Morbidity ◽  
Gastroesophageal Junction ◽  
Morbidity And Mortality ◽  
Term Survival ◽  
Long Term Survival ◽  
Nodal Dissection

Significant morbidity and mortality have historically been reported for surgical resection of gastric and gastroesophageal junction tumors. We evaluated our experience to determine morbidity and mortality and evaluated demographic and pathologic risk factors associated with postoperative outcome and long-term survival. A retrospective, Institutional Review Board-approved, single-institution database identified 102 patients who underwent resection with curative intent for gastroesophageal junction or gastric carcinoma from 2004 to 2012. The method of Kaplan and Meier was used to describe overall survival and estimate median survival. Of 102 patients, 74 were male and 28 were female. Of these, 24 patients were > 70 years of age at surgery (median = 62.9). Forty esophagectomies, 25 total gastrectomies, and 37 subtotal gastrectomies were performed. Two patients died (one esophagectomy and one gastrectomy). Forty-one developed a complication: 17 minor and 35 major, including six anastomotic leaks. Patients with low preoperative albumin ( P = 0.01) and increased age ( P = 0.05) were associated with having a postoperative complication; extent of nodal dissection ( P = 0.48), jejunostomy (0.24), performance status ( P = 0.77), type of surgery ( P = 0.74), and neoadjuvant therapy ( P = 0.24) were not associated. More extensive nodal dissection was associated with a decreased risk of death ( P = 0.007). Having any complication ( P = 0.20), an anastomotic leak ( P = 0.17), worse grade of complication ( P = 0.15), presence of feeding jejunostomy tube ( P = 0.17), and neoadjuvant therapy ( P = 0.30) were not associated with changes in overall survival. Thorough lymph node dissection improves survival without increasing postoperative morbidity. The data advocate for increased lymph node yield and close attention to nutritional support in gastroesophageal carcinoma patients.

Prognostic factors for survival in patients with advanced gastric cancer treated with chemotherapy.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 142-142
Author(s):  
Montserrat Mangas ◽  
Alberto Carmona Bayonas ◽  
Maria Luisa Sanchez Lorenzo ◽  
Avinash Ramchandani ◽  
Teresa Garcia ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Advanced Gastric Cancer ◽  
Group Performance ◽  
Gastroesophageal Junction ◽  
Cox Proportional Hazards Model ◽  
Her2 Status ◽  
Her2 Positive ◽  
Ecog Ps

142 Background: A prognostic model in advanced gastric cancer that integrates the Her2 status,histopathological classifications and other patient’s or treatment-dependent parameters is lacking. The aim is to identify clinicopathological factors for overall survival in a cohort of patients with advanced gastric cancer. Methods: 526 consecutive patients with advanced adenocarcinoma of the distal esophagus, gastroesophageal junction or stomach were analyzed. All patients were treated with poly-chemotherapy ( ≥ 2 drugs) at 19 Spanish and one Chilean centers between 2012 and 2015. Characteristics of patients, tumors, therapies and pathological factors, were analyzed by a Cox proportional hazards model. Results: The median overall survival was 10.3 months [95% confidence interval (CI), 9.5-11.1], and the time to progression was 6.7 months (95% CI, 6.1-7.2). Independent prognostic factors associated with overall survival were: distal non-diffuse histopathological subtype (hazard ratio, (HR) 0.73), Her2 positive 3+ (HR 0.54), Her2 positive 2+ with FISH + (HR 0.68), surgery of metastases (HR 0.34), Eastern Cooperative Group performance status (ECOG PS) 2 (HR 2.5), ECOG PS 3 (HR 7.37), and only distant lymph node metastases (HR 0.63) (Table 1). Conclusions: We have identified clinicopathological prognostic factors that could be important to stratify advanced gastric cancer, with potential implications in research and treatment. [Table: see text]

Combining prognostic value of nodal ratio and neutrophil to lymphocyte ratio in completely resected gastric cancer with D2 lymph node dissection.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15565-e15565
Author(s):  
Andres Guevara ◽  
Daniel Enriquez ◽  
Patricia Elizabeth Rioja ◽  
Christian Pacheco ◽  
Victor Castro ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Lymph Node ◽  
Neutrophil To Lymphocyte Ratio ◽  
Node Dissection ◽  
Early Disease ◽  
D2 Lymph Node Dissection ◽  
Lymphocyte Ratio ◽  
Nodal Ratio

e15565 Background: Outcomes in gastric cancer (GC) are still dismal even with complete D2 resection surgery and chemotherapy (CT), therefore identification of prognostic factors is critical to stratify patients at risk of recurrence or death. Nodal ratio (NR) has been recognized as a valuable prognostic factor and neutrophil to lymphocyte ratio (NLR) as systemic inflammation biomarker in some neoplasms. We evaluate overall survival (OS) combining NR and NLR among completely resected GC patients with D2 lymph node dissection in a Peruvian population. Methods: We reviewed retrospectively 791 medical records from GC pts with complete radical D2 resection between 2008 and 2012 at Instituto Nacional de Enfermedades Neoplasicas. We grouped according NR in < 0.2(Low), 0.2-0.5(Intermediate) and > 0.5(High), and NLR with cut-off < 3 and ≥3. We evaluated overall survival combining NR and NLR, also univariate and multivariate cox analysis were performed. OS was based on national registry and cannot evaluate DFS as long most patients return to their primary hospitals to follow-up. Results: Mean age was 60y [rank: 19-89]. Most frequent characteristics were distal localization (52.4%), intestinal subtype (52.6%) and poor differentiated histology (53%). From 791 patients, 156, 194 and 441 were diagnosed at I, II and III CS, respectively. Most patients had nodal involvement (66.8%), 21% and 28.4% received RT and CT, respectively. NLR < 3 was associated to early disease (p < 0.05). In nodal ratio groups, 68.9% had low, 23% intermediate and 8.1% high ratio, no differences were observed with NLR. At 5years median follow up, patients with NLR < 3 and low nodal ratio had better 5-year OS in this nodal group (71% vs 58% on NLR≥3; HR:0.75, 95%CI:0.49-0.94, p = 0.016]), and patients with intermediate and high nodal ratio had worse outcomes (25 and 15% 5year OS, respectively) without differences with NLR. Multivariate analysis showed higher nodal ratio had negative impact on OS. Conclusions: Neutrophil to lymphocyte ratio < 3 was associated to better OS in patients with low nodal ratio ( < 0.2), indeed this approach could be usefull to identify high risks patients with early disease in further studies.

Treatment patterns, effectiveness, and safety of Trastuzumab in Chinese patients with metastatic gastric cancer: Interim analysis of the EVIDENCE registry study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15595-e15595 ◽  
Author(s):  
Shukui Qin ◽  
Shen Lin ◽  
Ruihua Xu ◽  
Wuyun Su ◽  
Yong Tang ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Gastroesophageal Junction ◽  
Metastatic Gastric Cancer ◽  
Treatment Patterns ◽  
Chinese Patients ◽  
Registry Study ◽  
Her2 Positive ◽  
Real World Data ◽  
First Line Therapy ◽  
Gastroesophageal Junction Adenocarcinoma

e15595 Background: Trastuzumab (TRA) was approved for HER2-positive metastatic gastric or gastroesophageal junction adenocarcinoma (mGC) in China in August 2012. However, real-world data on the treatment patterns, effectiveness, and safety of TRA in Chinese patients (pts) with mGC are limited. Methods: EVIDENCE is a prospective, multicenter, non-interventional, registry study of 5 cohorts (NCT01839500). Cohort I enrolled pts with HER2-positive mGC (IHC3+ or IHC2+/ISH+) diagnosed up to 6 months previously. This interim analysis evaluated the effectiveness and safety of TRA in the first 95 pts of cohort I who were treated at 33 hospitals in China between April 2013 and August 15, 2016. Results: 71 of the 95 pts (74.7%) were male and the median age at diagnosis was 61 years (range 21-87 years). At the data cut-off date, the preliminary median PFS was 9.5 months (95% CI 7.6-11.8 months), and the preliminary median overall survival (OS) was 30.0 months (95% CI 18.6-38.7 months). 90 pts were treated with TRA + chemotherapy; XELOX (capecitabine + oxaliplatin) (28 pts, 31.1%) and capecitabine (20 pts, 22.2%) were the mostly commonly used regimens with TRA for first-line therapy, while paclitaxel was most commonly used with TRA for second-line (7.8%) and third-line (2.2%) therapy. TRA was also used in neoadjuvant (7 pts) and adjuvant (8 pts) settings prior to recurrence. During follow-up, 48 pts had progressive disease, and 21 (43.8%) received TRA beyond progression; 7 pts (14.6%) continued TRA after their 2nd disease progression. TRA-related adverse events (AEs) were observed in 26 pts (27.4%), including neutropenia in 10 pts (10.5%), thrombocytopenia in 9 (9.5%), and a decreased white blood cell count in 7 (7.4%). Only 6 pts (6.3%) experienced grade > = 3 TRA-related AEs (which included neutropenia and thrombocytopenia). Conclusions: In routine clinical practice in China, TRA combined with various chemotherapy regimens proved effective and well tolerated for treating mGC HER2+ pts. In addition to its use in palliative settings, TRA was also used as neoadjuvant/adjuvant treatment. Clinical trial information: NCT01839500.

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 Lymph node involvement in advanced gastroesophageal junction adenocarcinoma

2007 ◽  
Vol 134 (2) ◽  
pp. 378-385 ◽  
Author(s):  
Corrado Pedrazzani ◽  
Giovanni de Manzoni ◽  
Daniele Marrelli ◽  
Simone Giacopuzzi ◽  
Giovanni Corso ◽  
...  
Keyword(s):  
Lymph Node ◽  
Gastroesophageal Junction ◽  
Lymph Node Involvement ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
Node Involvement
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