Recent Advances in the Systemic Treatment of Localized Gastroesophageal Cancer

Summary: The addition of trastuzumab to neoadjuvant chemoradiotherapy did not improve disease-free survival for patients with HER2-overexpressing esophageal cancer. Trastuzumab did not increase toxicities, suggesting the potential for future studies combining it with other agents targeting HER2 in esophageal cancer.

LANCET ONCOLOGY (2022)

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Article Biology

FGFR Pathway Inhibition in Gastric Cancer: The Golden Era of an Old Target?

Csongor G. Lengyel et al.

Summary: Gastric cancer is the third leading cause of cancer-related death worldwide. Late diagnosis and lack of screening programs are major challenges. Novel diagnostic techniques and molecular pathways, such as the FGFR pathway, have been identified to improve survival in gastric cancer patients.

LIFE-BASEL (2022)

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Article Oncology

Tiragolumab plus atezolizumab versus placebo plus atezolizumab as a first-line treatment for PD-L1-selected non-small-cell lung cancer (CITYSCAPE): primary and follow-up analyses of a randomised, double-blind, phase 2 study

Byoung Chul Cho et al.

Summary: The combination of tiragolumab and atezolizumab showed promising efficacy and safety as first-line treatment for NSCLC, with improved objective response rate and progression-free survival compared to placebo plus atezolizumab.

LANCET ONCOLOGY (2022)

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Review Oncology

Role of CD155/TIGIT in Digestive Cancers: Promising Cancer Target for Immunotherapy

Daijun Wang et al.

Summary: The tumor microenvironment restricts immune cell function and survival by up-regulating inhibitory immune checkpoints, participating in tumor immune escape. Immunotherapies targeting immune checkpoints have provided options for cancer treatment. TIGIT, as a potential clinical target, interacts with CD155 on immune cells, mediating inhibitory immune regulation.

FRONTIERS IN ONCOLOGY (2022)

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Review Oncology

Claudin18.2 is a novel molecular biomarker for tumor-targeted immunotherapy

Weijie Cao et al.

Summary: CLDN18.2 protein, with limited expression in normal tissues and often abnormal expression in various primary malignant tumors, has become a potential specific marker for diagnosis and treatment of these tumors. Immunotherapy strategies targeting CLDN18.2, such as monoclonal antibodies, bispecific antibodies, CAR-T cells, and ADCs, have shown promising advancements in recent studies.

BIOMARKER RESEARCH (2022)

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Meeting Abstract Oncology

RATIONALE-306: Randomized, global, placebo-controlled, double-blind phase 3 study of tislelizumab plus chemotherapy versus chemotherapy as first-line treatment for advanced or metastatic esophageal squamous cell carcinoma (ESCC)

H. Yoon et al.

ANNALS OF ONCOLOGY (2022)

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Article Oncology

Oesophageal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up

R. Obermannova et al.

ANNALS OF ONCOLOGY (2022)

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Article Oncology

Gastric cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up

F. Lordick et al.

ANNALS OF ONCOLOGY (2022)

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Article Gastroenterology & Hepatology

Immunotherapy in MSI/dMMR tumors in the perioperative setting: The IMHOTEP trial

Clelia Coutzac et al.

Summary: The IMHOTEP trial aims to assess the efficacy of neoadjuvant anti-PD-1 treatment in localized MSI/dMMR tumors and explore molecular and immunological biomarkers predicting response to immune checkpoint inhibitors. This trial is significant in improving the outcomes of MSI/dMMR patients.

DIGESTIVE AND LIVER DISEASE (2022)

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Article Oncology

Choice of PD-L1 immunohistochemistry assay influences clinical eligibility for gastric cancer immunotherapy

Joe Yeong et al.

Summary: Our study showed that PD-L1 CPS scores and positivity rates are higher with the 28-8 assay compared to the 22C3 and other assays in GC PD-L1 IHC. Therefore, caution should be exercised in considering these assays as equivalent until stronger evidence of inter-assay concordance is established.

GASTRIC CANCER (2022)

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Article Oncology

Phase 2 study of trastuzumab deruxtecan in the neoadjuvant treatment for patients with HER2-positive gastric and gastroesophageal junction adenocarcinoma (EPOC2003).

Daisuke Takahari et al.

JOURNAL OF CLINICAL ONCOLOGY (2022)

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Article Oncology

Surgical and pathological outcome, and pathological regression, in patients receiving perioperative atezolizumab in combination with FLOT chemotherapy versus FLOT alone for resectable esophagogastric adenocarcinoma: Interim results from DANTE, a randomized, multicenter, phase IIb trial of the FLOT-AIO German Gastric Cancer Group and Swiss SAKK.

Salah-Eddin Al-Batran et al.

JOURNAL OF CLINICAL ONCOLOGY (2022)

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Article Oncology

Nimotuzumab plus concurrent chemo-radiotherapy versus chemo-radiotherapy in unresectable locally advanced esophageal squamous cell carcinoma (ESCC): Interim analysis from a prospective, randomized-controlled, double-blinded, multicenter, and phase III clinical trial (NXCEL1311 Study).

Xue Meng et al.

JOURNAL OF CLINICAL ONCOLOGY (2022)

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Article Oncology

Trial in progress: Phase 3 study of bemarituzumab + mFOLFOX6 versus placebo + mFOLFOX6 in previously untreated advanced gastric or gastroesophageal junction (GEJ) cancer with FGFR2b overexpression (FORTITUDE-101).

Elizabeth Catherine Smyth et al.

JOURNAL OF CLINICAL ONCOLOGY (2022)

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Article Oncology

Trial in progress: Phase 1b/3 study of bemarituzumab + mFOLFOX6 + nivolumab versus mFOLFOX6 + nivolumab in previously untreated advanced gastric and gastroesophageal junction (GEJ) cancer with FGFR2b overexpression (FORTITUDE-102).

Zev A. Wainberg et al.

JOURNAL OF CLINICAL ONCOLOGY (2022)

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Article Oncology

Perioperative ramucirumab in combination with FLOT versus FLOT alone for resectable esophagogastric adenocarcinoma (RAMSES/FLOT7) with high rate of signet cell component: Final results of the multicenter, randomized phase II/III trial of the German AIO and Italian GOIM.

Thorsten Oliver Goetze et al.

JOURNAL OF CLINICAL ONCOLOGY (2022)

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Article Surgery

Efficacy and Safety of Camrelizumab in Combination with Docetaxel

Zhongyi Dong et al.

Summary: This study aims to evaluate the efficacy and safety of camrelizumab in combination with docetaxel + S-1 in stage III gastric cancer patients who are EBV positive, with defective mismatch repair and CPS >= 5. The study design is a prospective, open-label, single-arm trial, and the primary outcome is the 3-year disease-free survival rate.

FRONTIERS IN SURGERY (2022)

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Article Oncology

1205MO Updated analysis of DESTINY-Gastric02: A phase II single-arm trial of trastuzumab deruxtecan (T-DXd) in western patients (Pts) with HER2-positive (HER2+) unresectable/metastatic gastric/gastroesophageal junction (GEJ) cancer who progressed on or after trastuzumab-containing regimen

G.Y. Ku et al.

ANNALS OF ONCOLOGY (2022)

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Article Oncology

ELEVATE - evaluating Temozolomide and Nivolumab in patients with advanced unresectable previously treated oesophagogastric adenocarcinoma with MGMT methylation: study protocol for a single arm phase II trial

Elizabeth Smyth et al.

Summary: This study aims to investigate the safety and biological effectiveness of administering Nivolumab after temozolomide treatment in patients with previously treated advanced oesophagogastric adenocarcinoma.

BMC CANCER (2022)

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Article Oncology

Bemarituzumab in patients with FGFR2b-selected gastric or gastro-oesophageal junction adenocarcinoma (FIGHT) : a randomised, double-blind, placebo-controlled, phase 2 study

Zev A. Wainberg et al.

Summary: This study investigated the efficacy and safety of bemarituzumab in combination with mFOLFOX6 for the treatment of HER2-negative advanced gastric or gastro-oesophageal junction adenocarcinomas. Although there was no statistically significant improvement in progression-free survival, bemarituzumab showed promising clinical efficacy.

LANCET ONCOLOGY (2022)

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Article Oncology

Prognostic and clinical significance of HER-2 low expression in early-stage gastric cancer

Tao Yang et al.

Summary: Gastric cancer is the fifth most common tumor worldwide. HER2-low expression in early-stage gastric cancer was associated with certain clinical characteristics, but did not have prognostic value for disease-free survival or overall survival.

BMC CANCER (2022)

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Article

Inherited Predisposition to Gastric Cancer

Sheila D. Rustgi et al.

Gastrointestinal Endoscopy Clinics of North America (2021)

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Article Oncology

FAST: a randomised phase II study of zolbetuximab (IMAB362) plus EOX versus EOX alone for first-line treatment of advanced CLDN18.2-positive gastric and gastro-oesophageal adenocarcinoma

U. Sahin et al.

Summary: This study demonstrates that adding zolbetuximab to first-line EOX treatment in advanced gastric cancer patients expressing CLDN18.2 can provide longer progression-free survival (PFS) and overall survival (OS). The therapy is generally well-tolerated with manageable adverse events.

ANNALS OF ONCOLOGY (2021)

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Article Oncology

Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

Hyuna Sung et al.

Summary: The global cancer burden in 2020 saw an estimated 19.3 million new cancer cases and almost 10.0 million cancer deaths. Female breast cancer surpassed lung cancer as the most commonly diagnosed cancer, while lung cancer remained the leading cause of cancer death. These trends are expected to rise in 2040, with transitioning countries experiencing a larger increase compared to transitioned countries due to demographic changes and risk factors associated with globalization and a growing economy. Efforts to improve cancer prevention measures and provision of cancer care in transitioning countries will be crucial for global cancer control.

CA-A CANCER JOURNAL FOR CLINICIANS (2021)

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Review Oncology

KEYNOTE-975 study design: a Phase III study of definitive chemoradiotherapy plus pembrolizumab in patients with esophageal carcinoma

Manish A. Shah et al.

Summary: This study describes the design and rationale of a trial investigating Pembrolizumab in combination with definitive chemoradiotherapy as first-line treatment in patients with locally advanced, unresectable esophageal/gastroesophageal junction cancer.

FUTURE ONCOLOGY (2021)

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Article Oncology

Ten-Year Outcome of Neoadjuvant Chemoradiotherapy Plus Surgery for Esophageal Cancer: The Randomized Controlled CROSS Trial

Ben M. Eyck et al.

Summary: The preoperative chemoradiotherapy regimen according to CROSS study has shown to have a long-term overall survival benefit for patients with locally advanced resectable esophageal or junctional cancer, with a stable effect observed up to 10 years of follow-up.

JOURNAL OF CLINICAL ONCOLOGY (2021)

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Article Medicine, General & Internal

Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer

Ronan J. Kelly et al.

Summary: In patients with resected esophageal or gastroesophageal junction cancer who had received neoadjuvant chemoradiotherapy, adjuvant therapy with nivolumab significantly improved disease-free survival compared to placebo.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

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Review Oncology

Immunotherapy Predictive Molecular Markers in Advanced Gastroesophageal Cancer: MSI and Beyond

Robin Park et al.

Summary: Biomarker research for immunotherapy in gastroesophageal cancer has experienced rapid development, with several biomarkers approved for clinical use but still imperfect in predicting responses. Novel biomarkers are showing promise for future clinical application, with a need for further development in this area. Current research is focused on evaluating and improving the predictive potential of immunotherapy biomarkers.

CANCERS (2021)

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Meeting Abstract Oncology

Trastuzumab deruxtecan (T-DXd) in patients (Pts) with HER2-positive gastric cancer (GC) or gastroesophageal junction (GEJ) adenocarcinoma who have progressed on or after a trastuzumab-containing regimen (DESTINY-gastric04, DG-04): A randomized phase III study

K. Shitara et al.

ANNALS OF ONCOLOGY (2021)

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Article Oncology

Trastuzumab in combination with 5-fluorouracil, leucovorin, oxaliplatin and docetaxel as perioperative treatment for patients with human epidermal growth factor receptor 2-positive locally advanced esophagogastric adenocarcinoma: A phase II trial of the Arbeitsgemeinschaft Internistische Onkologie Gastric Cancer Study Group

Ralf-Dieter Hofheinz et al.

Summary: The combination of trastuzumab and FLOT as perioperative treatment for locally advanced EGA has shown promising results, reaching a high rate of pathological complete response (pCR) and a good overall survival rate in HER-2 positive patients.

INTERNATIONAL JOURNAL OF CANCER (2021)

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Meeting Abstract Oncology

Neo-AEGIS (Neoadjuvant trial in Adenocarcinoma of the Esophagus and Esophago-Gastric Junction International Study): Preliminary results of phase III RCT of CROSS versus perioperative chemotherapy (Modified MAGIC or FLOT protocol). (NCT01726452).

John V. Reynolds et al.

JOURNAL OF CLINICAL ONCOLOGY (2021)

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Meeting Abstract Oncology

Pembrolizumab plus trastuzumab and chemotherapy for HER2+metastatic gastric or gastroesophageal junction (G/GEJ) cancer: Initial findings of the global phase 3 KEYNOTE-811 study.

Yelena Y. Janjigian et al.

JOURNAL OF CLINICAL ONCOLOGY (2021)

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Meeting Abstract Oncology

MATTERHORN: Efficacy and safety of neoadjuvant-adjuvant durvalumab and FLOT chemotherapy in resectable gastric and gastroesophageal junction cancer-A randomized, double-blind, placebo-controlled, phase 3 study.

Yelena Y. Janjigian et al.

JOURNAL OF CLINICAL ONCOLOGY (2021)

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Review Oncology

Role of Circulating Tumor DNA in Gastrointestinal Cancers: Current Knowledge and Perspectives

Emilie Moati et al.

Summary: Managing gastrointestinal (GI) cancers is a global challenge, with the need for new tools. Circulating tumor DNA (ctDNA) is a promising non-invasive biomarker that can help clinicians in various aspects of cancer management in the digestive oncology field. ctDNA shows potential in predicting treatment response, monitoring disease progression, and guiding personalized therapy in different GI cancers.

CANCERS (2021)

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Article Oncology

TremelImumab and Durvalumab Combination for the Non-OperatIve Management (NOM) of Microsatellite InstabiliTY (MSI)-High Resectable Gastric or Gastroesophageal Junction Cancer: The Multicentre, Single-Arm, Multi-Cohort, Phase II INFINITY Study

Alessandra Raimondi et al.

Summary: MSI-H status in GC/GEJC patients is prognostic and predictive, showing high sensitivity to immunotherapy and potential for achieving high rates of complete response with pre-operative treatment. The ongoing INFINITY study aims to investigate the role of immunotherapy in neoadjuvant or definitive treatment for MSI-H resectable GC/GEJC patients, potentially avoiding surgery in case of complete response.

CANCERS (2021)

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Review Oncology

Prognosis and Biological Behavior of Gastric Signet-Ring Cell Carcinoma Better or Worse: A Meta-Analysis

Shuai Zhao et al.

Summary: The prognosis of SRC is better at early stage compared to other types of gastric cancer, while it is relatively poorer at advanced stage.

FRONTIERS IN ONCOLOGY (2021)

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Article Oncology