Unanswered Questions in the Management of Gastroesophageal Junction Adenocarcinoma: An Overview from the Medical Oncologist's Perspective

2013 ◽  
pp. e155-e159
Author(s):  
Manish A. Shah
Keyword(s):  
Gastric Cancer ◽  
Treatment Options ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Preoperative Chemoradiotherapy ◽  
Phase Iii ◽  
Perioperative Chemotherapy ◽  
Two Phase ◽  
Multiple Treatment ◽  
Gastroesophageal Junction Adenocarcinoma

Patients with gastroesophageal junction (GEJ) adenocarcinoma have multiple treatment options; however, are victims of lack of consensus and wide variation in treatment, sometimes within the same hospital. While there is a consensus that surgery alone is inadequate for locally advanced disease, locoregional treatment has become the point for debate. Only in 2010 was the reclassification of GEJ cancers as esophageal cancers. Treatment options remain as varied as the classification of GEJ cancers: preoperative chemoradiotherapy, definitive chemoradiation, perioperative chemotherapy, and resection followed by postoperative chemoradiation. Several studies have examined the varying treatment paradigms; however, many fall short due to methodology or sample size. The MAGIC study determined perioperative chemotherapy to be an acceptable standard treatment option for patients with gastric cancer, althouth a significant portion of enrolled patients had distal esophageal and GEJ adenocarcinoma. The CROSS study concluded combination chemotherapy and radiation before resection beneficial. Preoperative therapy in cases of GEJ is beneficial for survival, but not as much impact is seen as in esophageal SCC, which exhibits an increased sensitivity to CRT. There is concurrence with two phase III studies from Japan and Korea on the role of adjuvant chemotherapy for gastric cancer. However, the applicability of these studies to GEJ adenocarcinoma remains a question, especially with the significantly different epidemiology of increased proximal and GEJ tumors in the West compared to Asia. To move forward with this increasingly prevalent disease, we will need to do more than understand the multiple treatment paradigms—we will need to select a strategy and examine it.

scholarly journals First-line pembrolizumab/placebo plus trastuzumab and chemotherapy in HER2-positive advanced gastric cancer: KEYNOTE-811

2020 ◽  
Author(s):  
Hyun Cheol Chung ◽  
Yung-Jue Bang ◽  
Charles S Fuchs ◽  
Shu-Kui Qin ◽  
Taroh Satoh ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Treatment Options ◽  
Gastroesophageal Junction ◽  
Phase Iii ◽  
First Line ◽  
Her2 Positive ◽  
Double Blind ◽  
Clinical Trial Registration ◽  
Gastroesophageal Junction Adenocarcinoma

Treatment options for patients with HER2-positive advanced gastric cancer are limited, and the prognosis for these patients is poor. Pembrolizumab has demonstrated promising antitumor activity in patients with advanced gastric or gastroesophageal junction adenocarcinoma as monotherapy, in combination with chemotherapy and in combination with trastuzumab. Combining pembrolizumab with trastuzumab and chemotherapy may therefore provide a benefit for patients with advanced HER2-positive gastric cancer. Here we aimed to describe the design of and rationale for the randomized, double-blind, placebo-controlled Phase III KEYNOTE-811 study, which will evaluate the efficacy and safety of pembrolizumab or placebo in combination with trastuzumab and chemotherapy as first-line treatment for patients with advanced HER2-positive gastric or gastroesophageal junction adenocarcinoma. Clinical trial registration: NCT03615326 ( ClinicalTrials.gov )

Multicenter Phase II Trial of S-1 Plus Cisplatin in Patients With Untreated Advanced Gastric or Gastroesophageal Junction Adenocarcinoma

2006 ◽  
Vol 24 (4) ◽  
pp. 663-667 ◽  
Author(s):  
Jaffer A. Ajani ◽  
Fa-Chyi Lee ◽  
Deepti A. Singh ◽  
Daniel G. Haller ◽  
Heinz-Josef Lenz ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Gastroesophageal Junction ◽  
Median Number ◽  
Phase Iii ◽  
Highly Active ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
Gastric Cancer Patients

Purpose S-1 plus cisplatin is considered highly active in Japanese gastric cancer patients. We conducted a phase II multi-institutional trial, in the West, in patients with untreated advanced gastric or gastroesophageal junction adenocarcinoma to evaluate activity and safety of this combination. Methods Patients received cisplatin intravenously at 75 mg/m2 on day 1 and S-1 orally at 25 mg/m2/dose bid (50 mg/m2/d) on days 1 to 21, repeated every 28 days. Patients with histologic proof of gastric or gastroesophageal junction adenocarcinoma with a Karnofsky performance status (KPS) of ≥ 70% and near-normal organ function were eligible. All patients provided a written informed consent. To observe a 45% confirmed overall response rate (ORR), 41 assessable patients were needed. Results All 47 patients were assessed for safety and survival, and 41 patients were assessed for ORR. The median age was 56 years and median KPS was 80%. The median number of chemotherapy cycles was four. The confirmed ORR was 51% (95% CI, 35% to 67%) and it was 49% by an independent review. At the 6-month interval, 71% of patients were alive, with a median survival time of 10.9 months. Frequent grade 3 or 4 toxicities included fatigue (26%), neutropenia (26%), vomiting (17%), diarrhea (15%), and nausea (15%); however, stomatitis (2%) and febrile neutropenia (2%) were uncommon. There was one (2%) treatment-related death. Conclusion S-1 plus cisplatin is active against gastric cancer and has a favorable toxicity profile. A global phase III study of S-1 plus cisplatin versus fluorouracil plus cisplatin currently is accruing patients.

scholarly journals PERIOPERATIVE CHEMOTHERAPY IN LOCALLY ADVANCED GASTRIC CANCER

2013 ◽  
Vol 50 (3) ◽  
pp. 236-242 ◽  
Author(s):  
Thales Paulo BATISTA ◽  
Candice Amorim de Araujo Lima SANTOS ◽  
Gustavo Fernandes Godoy ALMEIDA
Keyword(s):  
Gastric Cancer ◽  
Therapeutic Strategy ◽  
Multimodal Therapy ◽  
Standard Treatment ◽  
Treatment Options ◽  
Locally Advanced ◽  
Special Focus ◽  
Perioperative Chemotherapy ◽  
Locally Advanced Gastric Cancer ◽  
Advanced Stages

Gastric cancer is one of the most common cancers and a main cause of cancer-related death worldwide, since the majority of patients suffering of this malignancy are usually faced with a poor prognosis due to diagnosis at later stages. In order to improve treatment outcomes, the association of surgery with chemo and/or radiotherapy (multimodal therapy) has become the standard treatment for locally advanced stages. However, despite several treatment options currently available for management of these tumors, perioperative chemotherapy has been mainly accepted for the comprehensive therapeutic strategy including an appropriated D2-gastrectomy. This manuscript presents a (nonsystematic) critical review about the use of perioperative chemotherapy, with a special focus on the drugs delivery.

scholarly journals RACE-trial: neoadjuvant radiochemotherapy versus chemotherapy for patients with locally advanced, potentially resectable adenocarcinoma of the gastroesophageal junction - a randomized phase III joint study of the AIO, ARO and DGAV

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Sylvie Lorenzen ◽  
Alexander Biederstädt ◽  
Ulrich Ronellenfitsch ◽  
Christoph Reißfelder ◽  
Stefan Mönig ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Preoperative Chemotherapy ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Neoadjuvant Radiochemotherapy ◽  
Perioperative Chemotherapy ◽  
Free Survival ◽  
Link Type

Abstract Background Despite obvious advances over the last decades, locally advanced adenocarcinomas of the gastroesophageal junction (GEJ) still carry a dismal prognosis with overall 5-year survival rates of less than 50% even when using modern optimized treatment protocols such as perioperative chemotherapy based on the FLOT regimen or radiochemotherapy. Therefore the question remains whether neoadjuvant chemotherapy or neoadjuvant radiochemotherapy is eliciting the best results in patients with GEJ cancer. Hence, an adequately powered multicentre trial comparing both therapeutic strategies is clearly warranted. Methods The RACE trial is a an investigator initiated multicenter, prospective, randomized, stratified phase III clinical trial and seeks to investigate the role of preoperative induction chemotherapy (2 cycles of FLOT: 5-FU, leucovorin, oxaliplatin, docetaxel) with subsequent preoperative radiochemotherapy (oxaliplatin weekly, 5-FU plus concurrent fractioned radiotherapy to a dose of 45 Gy) compared to preoperative chemotherapy alone (4 cycles of FLOT), both followed by resection and postoperative completion of chemotherapy (4 cycles of FLOT), in the treatment of locally advanced, potentially resectable adenocarcinoma of the gastroesophageal junction. Patients with cT3–4, any N, M0 or cT2 N+, M0 adenocarcinoma of the GEJ are eligible for inclusion. The RACE trial aims to enrol 340 patients to be allocated to both treatment arms in a 1:1 ratio stratified by tumour site. The primary endpoint of the trial is progression-free survival assessed with follow-up of maximum 60 months. Secondary endpoints include overall survival, R0 resection rate, number of harvested lymph nodes, site of tumour relapse, perioperative morbidity and mortality, safety and toxicity and quality of life. Discussion The RACE trial compares induction chemotherapy with FLOT followed by preoperative oxaliplatin and 5-Fluorouracil-based chemoradiation versus preoperative chemotherapy with FLOT alone, both followed by surgery and postoperative completion of FLOT chemotherapy in the treatment of locally advanced, non-metastatic adenocarcinoma of the GEJ. The trial aims to show superiority of the combined chemotherapy/radiochemotherapy treatment, assessed by progression-free survival, over perioperative chemotherapy alone. Trial registration ClinicalTrials.gov; NCT04375605; Registered 4th May 2020;

A single-arm, phase II feasibility study of neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) chemotherapy in potentially resectable gastric or gastroesophageal junction adenocarcinoma.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 96-96
Author(s):  
M. Ryu ◽  
Y. Choi ◽  
B. Kim ◽  
Y. Park ◽  
H. Kim ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Advanced Gastric Cancer ◽  
Residual Disease ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Phase Iii ◽  
R0 Resection ◽  
Locally Advanced Gastric Cancer ◽  
Grade 3

96 Background: The aim of this study was to evaluate feasibility and safety of neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) chemotherapy in patients with potentially resectable adenocarcinoma of stomach or gastroesophageal junction. Methods: Forty-one patients with clinical stage T3-4N0M0 or T2-4N+M0 determined by CT, endoscopic ultrasonography, and laparoscopy were enrolled between DEC 2008 and MAR 2010. Gastrectomy with D2 lymph node dissection was conducted after 3 cycles of DOS chemotherapy. DOS chemotherapy consists of docetaxel 50 mg/m2 iv (day1), oxaliplatin 100 mg/m2 iv (day1), and S-1 40 mg/m2 po bid (days1-14) at 3 weeks interval. After curative gastrectomy, the patients were given 1 year of adjuvant chemotherapy with S-1 (40 mg/m2 D1-28, every 6 weeks). Results: All patients finished the planned neoadjuvant chemotherapy. Twenty-three (56%) patients achieved a partial response, and the remaining 18 patients had stable disease by CT scan after 3 cycles of DOS chemotherapy. No disease progression was observed during the neoadjuvant chemotherapy. A median 4.7 weeks (range, 4.0-7.6) after the start of the 3rd cycle of DOS chemotherapy, 39 (95%) patients underwent R0 resection with no pathologic residual disease in 4 (10%) patients. Hematologic toxicities were common including grade 4 neutropenia (32%), grade 3 thrombocytopenia (17%), and febrile neutropenia (10%). However, hematologic toxicities were generally transient and manageable. There were no grade 3 or 4 non-hematologic toxicities with frequency > 5% of patients. With all toxicities taken together, 21 (51%) patients experienced grade 3 or 4 toxicities (except grade 3 neutropenia). There was no treatment-related death, and surgical complications included only mild wound problem in 4 (10%) patients. Conclusions: In this study, neoadjuvant DOS chemotherapy could induce a sufficient down-staging and R0 resection of locally advanced gastric cancer with mild and manageable toxicities. A phase III randomized trial is planned for evaluating the benefit of neoadjuvant DOS chemotherapy in patients with locally advanced gastric cancer. [Table: see text]

Phase III study of first-line zolbetuximab + CAPOX versus placebo + CAPOX in Claudin 18.2+/HER2−advanced or metastatic gastric or gastroesophageal junction adenocarcinoma: GLOW.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS4648-TPS4648
Author(s):  
Manish A. Shah ◽  
Jaffer A. Ajani ◽  
Salah-Eddin Al-Batran ◽  
Yung-Jue Bang ◽  
Daniel Catenacci ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Locally Advanced ◽  
Phase Iii ◽  
Controlled Study ◽  
Her2 Status ◽  
First Line ◽  
Double Blind ◽  
Junction Protein

TPS4648 Background: Gastric cancer is the fourth leading cause of cancer death worldwide. Capecitabine + oxaliplatin (CAPOX) is a standard first-line treatment for advanced gastric cancer. Claudin (CLDN)18.2 has emerged as a promising targetable biomarker. In healthy tissue, CLDN18.2, a tight junction protein, is confined to gastric mucosa (ie, cells in the pit and base regions of gastric glands). Upon malignant transformation, structural loss in gastric or gastroesophageal junction (G/GEJ) adenocarcinoma cells may allow antibodies more access to previously unavailable CLDN18.2. Zolbetuximab is a chimeric IgG1 monoclonal antibody that specifically binds to CLDN18.2 and mediates cell death through antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Results of a phase 2 study (NCT01630083) showed prolonged survival of patients with CLDN18.2-positive (CLDN18.2+) advanced G/GEJ adenocarcinoma treated with zolbetuximab + epirubicin, oxaliplatin, and capecitabine (EOX) vs EOX alone. Methods: This phase 3, double-blind, placebo-controlled study (NCT03653507) will enroll ~500 adult patients from global sites. Patients are required to have CLDN18.2+/HER2− locally advanced unresectable or metastatic G or GEJ adenocarcinoma that is radiographically evaluable per RECIST v1.1. Patients are not permitted to have received prior treatment with chemotherapy for advanced or metastatic G or GEJ adenocarcinoma. Patients will be randomly assigned 1:1 to receive either zolbetuximab plus CAPOX or placebo plus CAPOX. Randomization will be stratified by region (Asia vs non-Asia), number of metastatic sites (0 to 2 vs ≥3), and prior gastrectomy (yes vs no). Zolbetuximab will be administered at a loading dose of 800 mg/m2 IV on Cycle 1 Day 1 followed by 600 mg/m2 IV every 3 weeks. Central testing of tumor tissue will determine CLDN18.2 and HER2 status (if unknown); patients will be considered CLDN18.2+ if ≥75% of tumor cells demonstrate moderate-to-strong membranous immunohistochemical staining. The primary objective is to compare progression-free survival between treatment arms. Secondary endpoints are overall survival; objective response rate; duration of response; and the safety/tolerability, pharmacokinetics, and immunogenicity of zolbetuximab. As of January 31, 2020, 127 sites were active and open to enrollment. Clinical trial information: NCT03653507 .

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 Perioperative chemotherapy for gastric cancer: the current state

2018 ◽  
Vol 20 (2) ◽  
pp. 56-60
Author(s):  
V K Lyadov ◽  
O A Pardabekova ◽  
M A Lyadova
Keyword(s):  
Gastric Cancer ◽  
Malignant Tumors ◽  
Locally Advanced ◽  
High Rate ◽  
Phase Iii ◽  
Perioperative Chemotherapy ◽  
Phase Iii Trial ◽  
Locally Advanced Gastric Cancer ◽  
Current State ◽  
Resectable Gastric Cancer

Gastric cancer has one of the leading positions in the world in the prevalence and mortality among malignant tumors. The results of surgical treatment of locally advanced gastric cancer remain generally poor due to the high rate of relapse after surgery. Currently, perioperative (pre- and postoperative) chemotherapy in combination with surgery is recommended for patients with stage ≥IB resectable gastric cancer. We analyzed the studies devoted to the problem of choosing the optimal regimen of perioperative chemotherapy in locally advanced and oligometastatic gastric cancer. The highest efficacy was observed in the taxan-containing regimen FLOT which allowed to increase the median overall survival up to 50 months in a randomized controlled phase III trial. The use of perioperative chemotherapy with anti-Her2 therapy, immunotherapy or any other biologic drug remains investigational.

scholarly journals The role of pembrolizumab in the treatment of PD-L1 expressing gastric and gastroesophageal junction adenocarcinoma

2019 ◽  
Vol 12 ◽  
pp. 175628481986976 ◽  
Author(s):  
Gagandeep Brar ◽  
Manish A. Shah
Keyword(s):  
Gastric Cancer ◽  
Immune Checkpoint Inhibitors ◽  
Standard Treatment ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Gastroesophageal Junction ◽  
Response To Treatment ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
Tumor Types

Gastric cancer is a leading cause of cancer-related death worldwide. Recent evidence suggests that gastric cancer is a complex and heterogenous disease with emerging subtypes shown to affect response to treatment and survival. Immunotherapy is an advancing field and immune checkpoint inhibitors have become standard treatment options in numerous tumor types. In this review, we discuss the current and evolving use of checkpoint blockade, focusing on the anti-PD-1 inhibitor, pembrolizumab, for use in advanced gastric and gastroesophageal cancers.

Perioperative chemotherapy alone versus preoperative chemoradiotherapy for locally advanced distal esophageal and gastroesophageal junction cancer: A 10-year review of the British Columbia (BC) Cancer Registry.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4028-4028
Author(s):  
Shiru Lucy Liu ◽  
Irene S. Yu ◽  
Sally CM Lau ◽  
Yizhou Zhao ◽  
Devin Schellenberg ◽  
...  
Keyword(s):  
Cancer Registry ◽  
Performance Status ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Preoperative Chemoradiotherapy ◽  
Pathologic Response ◽  
R0 Resection ◽  
Perioperative Chemotherapy ◽  
Cancer Specific Survival ◽  
Significant Difference

4028 Background: The optimal treatment strategy for resectable cancer of the distal esophagus (ESOPH) and gastroesophageal junction (GEJ) remains controversial. This study evaluates patterns of practice in BC, rates of complete surgical resection, and survival outcomes of patients treated with perioperative chemotherapy alone (CA), per MAGIC or FLOT4 protocol, versus preoperative chemoradiotherapy (CRT), per CROSS protocol. Methods: We undertook a provincial analysis of initially resectable, locally advanced, cancer of the ESOPH and/or GEJ who underwent surgery in BC, from 2008 to 2018. Baseline patient, tumor, treatment, and clinical outcome data were collected from the BC Cancer Registry. Kaplan-Meier survival and multivariate regression analyses were conducted. Results: Among 575 patients, 468 underwent surgery and were included (Table). More surgeries were aborted intraoperatively in the CA cohort compared to CRT (12% vs 2%, p<0.001). There was no difference in age, sex, or ECOG performance status among the cohorts, and 83% were adenocarcinoma. While 82% of ESOPH involving GEJ (N = 251, 54%) is treated with CRT, only 53% of GEJ alone (N=217, 46%) is treated with CRT (p<0.001). CRT is associated with a higher rate of complete or partial pathologic response compared to CA (59% vs 39%, p=0.002). R0 resection rate was 90% and 94% in the CA and CRT cohort, respectively (p=0.383). There is no statistically significant difference in overall survival, with medians of 29.6 and 26.0 months for patients treated with CA and CRT, respectively (p=0.723). Cancer-specific survival is also not significantly different (p=0.565). In the CA cohort, 37% of patients complete all 8 cycles of FLOT and 52% of patients complete all 6 cycles of MAGIC (p=0.396). Conclusions: Patients treated with CRT have higher rates of complete resection and pathologic response, but their survival is not significantly different compared to those treated with CA. [Table: see text]

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