4.3 Review

New developments and standard of care in the management of advanced gastric cancer

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Article Oncology

Trastuzumab Deruxtecan in Anti-Human Epidermal Growth Factor Receptor 2 Treatment-Naive Patients With Human Epidermal Growth Factor Receptor 2-Low Gastric or Gastroesophageal Junction Adenocarcinoma: Exploratory Cohort Results in a Phase II Trial

Kensei Yamaguchi et al.

Summary: This study aimed to investigate the efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients with HER2-low gastric or gastroesophageal junction adenocarcinoma. The results showed that T-DXd has clinical activity in heavily pretreated patients with HER2-low gastric/GEJ adenocarcinoma.

JOURNAL OF CLINICAL ONCOLOGY (2023)

Article Medicine, General & Internal

Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro- oesophageal junction adenocarcinoma (SPOTLIGHT) : a multicentre, randomised, double-blind, phase 3 trial

Kohei Shitara et al.

Summary: Zolbetuximab in combination with mFOLFOX6 significantly prolongs progression-free survival and overall survival in patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma, with good safety profile.

LANCET (2023)

Article Oncology

Trastuzumab deruxtecan in patients in the USA and Europe with HER2-positive advanced gastric or gastroesophageal junction cancer with disease progression on or after a trastuzumab-containing regimen (DESTINY-Gastric02) : primary and updated analyses from a single-arm, phase 2

Eric Van Cutsem et al.

Summary: The DESTINY-Gastric02 trial is a phase 2 study evaluating the efficacy of trastuzumab deruxtecan in HER2-positive advanced gastric and gastro-oesophageal junction cancer. The results demonstrate clinically meaningful response rates, supporting its use as second-line therapy for these patients.

LANCET ONCOLOGY (2023)

Article Biochemistry & Molecular Biology

Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial

Manish A. Shah et al.

Summary: The GLOW trial demonstrated that zolbetuximab, a monoclonal antibody targeting CLDN18.2, combined with CAPOX, significantly improved progression-free survival and overall survival in patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma.

NATURE MEDICINE (2023)

Article Oncology

Nivolumab plus chemotherapy versus placebo plus chemotherapy in patients with HER2-negative, untreated, unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer (ATTRACTION-4): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial

Yoon-Koo Kang et al.

Summary: This study investigated the efficacy of nivolumab plus oxaliplatin-based chemotherapy for HER2-negative, unresectable, advanced or recurrent gastric or gastro-oesophageal junction cancer, showing a significant improvement in progression-free survival but not overall survival in Asian patients. The combination therapy may potentially serve as a new first-line treatment option for these patients.

LANCET ONCOLOGY (2022)

Article Medicine, General & Internal

Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer

J. Cortes et al.

Summary: Among patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane, trastuzumab deruxtecan was associated with a lower risk of disease progression or death compared to trastuzumab emtansine. However, treatment with trastuzumab deruxtecan was associated with interstitial lung disease and pneumonitis.

NEW ENGLAND JOURNAL OF MEDICINE (2022)

Review Pharmacology & Pharmacy

Trastuzumab Deruxtecan-Induced Interstitial Lung Disease/Pneumonitis in ERBB2-Positive Advanced Solid Malignancies: A Systematic Review

Ziad Abuhelwa et al.

Summary: This systematic review examines the incidence, severity, and management of interstitial lung disease (ILD) or pneumonitis induced by the drug T-DXd. The overall incidence of ILD/pneumonitis cases was found to be 11.40%, with the majority being grade 1 or 2. Further studies are needed to identify risk factors and develop effective management strategies.
Article Medicine, General & Internal

Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer

Shanu Modi et al.

Summary: Trastuzumab deruxtecan demonstrated significantly longer progression-free and overall survival compared to physician's choice chemotherapy in patients with HER2-low metastatic breast cancer.

NEW ENGLAND JOURNAL OF MEDICINE (2022)

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)

Article Oncology

Phase III Trial of Avelumab Maintenance After First-Line Induction Chemotherapy Versus Continuation of Chemotherapy in Patients With Gastric Cancers: Results From JAVELIN Gastric 100

Markus Moehler et al.

Summary: The use of avelumab as maintenance therapy after first-line chemotherapy did not show superior overall survival compared to continued chemotherapy in patients with advanced GC or GEJC, regardless of PD-L1 status. Treatment-related adverse events occurred in both groups, with more severe events in the continued chemotherapy group.

JOURNAL OF CLINICAL ONCOLOGY (2021)

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)

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)

Article Multidisciplinary Sciences

The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer

Yelena Y. Janjigian et al.

Summary: The study results demonstrate that adding pembrolizumab to trastuzumab and chemotherapy significantly reduces tumor size, induces complete responses in some patients, and improves objective response rate in HER2-positive gastric or gastro-oesophageal junction adenocarcinoma.

NATURE (2021)

Article Oncology

Phase III Study to Evaluate Efficacy and Safety of Andecaliximab With mFOLFOX6 as First-Line Treatment in Patients With Advanced Gastric or GEJ Adenocarcinoma (GAMMA-1)

Manish A. Shah et al.

Summary: In patients with untreated human epidermal growth factor receptor 2-negative gastric or GEJ adenocarcinoma, the addition of ADX to mFOLFOX6 did not improve overall survival.

JOURNAL OF CLINICAL ONCOLOGY (2021)

Article Oncology

Predictive role of microsatellite instability for PD-1 blockade in patients with advanced gastric cancer: a meta-analysis of randomized clinical trials

F. Pietrantonio et al.

Summary: Several post hoc analyses of RCTs have shown the importance of MSI as a predictive factor for immunotherapy in patients with advanced GC, particularly in those with MSI-high status. This suggests that MSI status may play a significant role in the treatment of GC and warrants further investigation.

ESMO OPEN (2021)

Article Medicine, General & Internal

First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial

Yelena Y. Janjigian et al.

Summary: Nivolumab plus chemotherapy showed superior overall survival and progression-free survival compared to chemotherapy alone in previously untreated patients with advanced gastric, gastro-oesophageal junction, or oesophageal adenocarcinoma, indicating it as a new standard first-line treatment option with acceptable safety profile.

LANCET (2021)

Article Medicine, General & Internal

Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer

Kohei Shitara et al.

NEW ENGLAND JOURNAL OF MEDICINE (2020)

Article Gastroenterology & Hepatology

Clinical impact of intratumoral HER2 heterogeneity on trastuzumab efficacy in patients with HER2-positive gastric cancer

Takeru Wakatsuki et al.

JOURNAL OF GASTROENTEROLOGY (2018)

Article Multidisciplinary Sciences

Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade

Dung T. Le et al.

SCIENCE (2017)

Review Oncology

Antibody drug conjugates and bystander killing: is antigen-dependent internalisation required?

Alexander H. Staudacher et al.

BRITISH JOURNAL OF CANCER (2017)

Article Medicine, General & Internal

PD-1 Blockade in Tumors with Mismatch-Repair Deficiency

D. T. Le et al.

NEW ENGLAND JOURNAL OF MEDICINE (2015)

Article Medicine, General & Internal

Randomized Trial of TAS-102 for Refractory Metastatic Colorectal Cancer

Robert J. Mayer et al.

NEW ENGLAND JOURNAL OF MEDICINE (2015)

Article Medicine, General & Internal

Capecitabine and oxaliplatin for advanced esophagogastric cancer

David Cunningham et al.

NEW ENGLAND JOURNAL OF MEDICINE (2008)