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Esophageal Adenocarcinoma
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Related cancers:
6d
TRIFLUOX-DP: Safety of Trifluridine/Tipiracil in Patients With Dihydropyrimidine Dehydrogenase Deficiency Diagnosed With Metastatic Colorectal or Gastroesophageal Cancer (clinicaltrials.gov)
P2, N=73, Not yet recruiting, UNICANCER | Initiation date: Oct 2024 --> Jan 2025
Trial initiation date • Metastases
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Opdivo (nivolumab) • Avastin (bevacizumab) • Herceptin (trastuzumab) • 5-fluorouracil • Vectibix (panitumumab) • capecitabine • oxaliplatin • Lonsurf (trifluridine/tipiracil)
6d
BGB-53038-101: A First-in-human Study of BGB-53038, a Pan-KRAS Inhibitor, Alone or in Combinations in Participants With Advanced or Metastatic Solid Tumors With KRAS Mutations or Amplification (clinicaltrials.gov)
P1, N=177, Recruiting, BeiGene | Not yet recruiting --> Recruiting
Enrollment open • Metastases
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Erbitux (cetuximab) • Tevimbra (tislelizumab-jsgr)
6d
METAGIO: Observational Study of Patients Treated With Nivolumab and Chemotherapy for Advanced or Metastatic Esophageal, Gastroesophageal or Gastric Cancer in France (clinicaltrials.gov)
P=N/A, N=500, Recruiting, Bristol-Myers Squibb | Not yet recruiting --> Recruiting | Initiation date: Aug 2024 --> Dec 2024
Enrollment open • Trial initiation date • Metastases
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Opdivo (nivolumab)
7d
Expression of therapy target molecules in esophagogastric junction and Barrett's adenocarcinoma. (PubMed, Gastric Cancer)
Most EGJ and Barrett's adenocarcinomas may be eligible for molecular targeted therapy. Appropriate patient stratification based on these molecular tests will be important for precision medicine of the EGJ and Barrett's adenocarcinoma.
Journal • PD(L)-1 Biomarker • IO biomarker
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HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • CLDN18 (Claudin 18)
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HER-2 positive • HER-2 amplification • HER-2 expression • PD-L1 expression + HER-2 overexpression
11d
The role of perioperative chemoimmunotherapy in the treatment of potentially resectable MSI-H gastric adenocarcinoma - a case report. (PubMed, Rozhl Chir)
This case report supports the potential importance of immunotherapy in the treatment of resectable locally advanced MSI-H gastric cancer, which is currently being evaluated in clinical trials.
Journal
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MSI (Microsatellite instability)
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MSI-H/dMMR
12d
A phase II study evaluating safety and efficacy of niraparib in patients with previously treated homologous recombination defective metastatic esophageal/gastroesophageal junction/proximal gastric adenocarcinoma. (PubMed, Front Oncol)
The most common adverse events seen were anemia, fatigue, and thrombocytopenia. In patients with metastatic EAC, single agent niraparib as second line therapy is not an effective option.
P2 data • Journal • Metastases
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ARID1A (AT-rich interaction domain 1A) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • GEN1 (GEN1 Holliday junction 5' flap endonuclease) • PARP2 (Poly(ADP-Ribose) Polymerase 2)
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FANCA deletion
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Zejula (niraparib)
13d
ARM-GI: Radiation Therapy for the Treatment of Metastatic Gastrointestinal Cancers (clinicaltrials.gov)
P=N/A, N=28, Recruiting, University of California, San Francisco | Trial completion date: Nov 2026 --> Nov 2027 | Trial primary completion date: Dec 2024 --> Dec 2025
Trial completion date • Trial primary completion date • Metastases
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MSI (Microsatellite instability) • PD-1 (Programmed cell death 1)
14d
Esophageal submucosal gland duct adenoma: An unrecognised esophageal counterpart of minor salivary gland tumours with frequent BRAF V600E mutations. (PubMed, Histopathology)
This study delineates a distinct subtype of benign adenoma arising from the esophageal submucosal gland duct, characterised by multiple lobulated cystic proliferation of benign epithelial layers within the submucosa. BRAF V600E mutations were present, similar to in sialadenoma papilliferum. We determined the genetic mutation present in esophageal submucosal gland duct adenoma, providing further evidence that it is an esophageal counterpart of minor salivary gland tumours.
Journal
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BRAF (B-raf proto-oncogene) • CDX2 (Caudal Type Homeobox 2) • KRT19 (Keratin 19) • MUC2 (Mucin 2) • MUC5AC (Mucin 5AC) • MUC6 (Mucin 6)
|
BRAF V600E • BRAF V600
20d
A Phase I Study of [177Lu]Lu-FF58 in Patients With Advanced Solid Tumors. (clinicaltrials.gov)
P1, N=6, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Jan 2027 --> Dec 2024 | Trial primary completion date: Jan 2027 --> Dec 2024
Trial completion date • Trial primary completion date • Metastases
22d
ZWI-ZW25-101: Trial of ZW25 (Zanidatamab) in Patients With Advanced HER2-expressing Cancers (clinicaltrials.gov)
P1, N=279, Completed, Jazz Pharmaceuticals | Active, not recruiting --> Completed
Trial completion • Metastases
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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HER-2 positive • HER-2 overexpression • EGFR wild-type • KRAS wild-type • ALK wild-type • RAS wild-type • ALK-ROS1 fusion • HER-2 positive + HER-2 overexpression • HER-2 positive + RAS wild-type
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paclitaxel • capecitabine • Tukysa (tucatinib) • vinorelbine tartrate • Ziihera (zanidatamab-hrii)
22d
Clinical application of capsule sponge testing in symptomatic reflux disease: a national prospective cohort study. (PubMed, BMC Gastroenterol)
Capsule sponge testing is effectively at identifying the 30% of symptomatic reflux patients requiring further investigation with UGI endoscopy and aiding the diagnosis of Barrett's oesophagus in clinical practice. Judicious follow-up of the discharged group will be critical to validate the ongoing use of capsule sponge testing long-term.
Journal
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TFF3 (Trefoil factor 3)
26d
Plasma DNA methylation detection for early screening, diagnosis, and monitoring of esophageal adenocarcinoma and squamous cell carcinoma. (PubMed, World J Gastroenterol)
According to our findings, plasma SHOX2, SEPTIN9, RNF180, and EPO methylation exhibits appreciated sensitivity for diagnosing EC. The precise measurement of plasma SHOX2, SEPTIN9, RNF180, and EPO methylation can improve EC diagnosis and therapy efficacy monitoring.
Journal • Epigenetic controller
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SEPTIN9 (Septin 9) • SHOX2 (SHOX Homeobox 2)
28d
A Phase II Trial to Evaluate the Effect of Itraconazole on Pathologic Complete Response Rates in Resectable Esophageal Cancer (clinicaltrials.gov)
P2, N=78, Recruiting, VA Office of Research and Development | Not yet recruiting --> Recruiting
Enrollment open
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itraconazole
29d
Effects of Neoadjuvant Therapy on Tumour Target Expression of Oesophageal Cancer Tissue for NIR Fluorescence Imaging. (PubMed, Mol Imaging Biol)
EpCAM and EGFR appear to be the most suitable targets for tumour-specific NIR fluorescence imaging of oesophageal adenocarcinoma and squamous cell carcinoma, respectively. Unaffected expression of all suitable markers by neoadjuvant therapy implies that the diagnostic biopsy can be used to select a patient-specific target for response evaluation by molecular imaging.
Journal
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EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase) • EPCAM (Epithelial cell adhesion molecule)
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EPCAM expression
29d
Liquid biopsy to identify Barrett's oesophagus, dysplasia and oesophageal adenocarcinoma: the EMERALD multicentre study. (PubMed, Gut)
Using a comprehensive approach integrating unbiased genome-wide biomarker discovery and several independent experimental validations, we have developed and validated a novel blood test that might complement screening options for BE/EAC.
Journal • Liquid biopsy • Biopsy
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MIR21 (MicroRNA 21) • MIR18A (MicroRNA 18a) • MIR106B (MicroRNA 106b) • MIR15A (MicroRNA 15a) • MIR93 (MicroRNA 93)
1m
PD-L1 thresholds predict efficacy of immune checkpoint inhibition in first-line treatment of advanced gastroesophageal adenocarcinoma. A systematic review and meta-analysis of seven phase III randomized trials. (PubMed, ESMO Open)
The present meta-analysis confirmed that the benefit of PD-1 blockade in GEA patients is related to PD-L1 CPS, with increased benefit observed for higher CPS cut-offs and no OS benefit in the CPS <1 subset. Overall, data indicate that PD-L1 CPS ≥5 could represent an acceptable cut-off to optimize the risk/benefit ratio of such agents. Our data suggest a potential clinical benefit of immunotherapy in selected patients within the CPS 1-4 population which needs further investigation.
P3 data • Retrospective data • Review • Journal • Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker • Metastases
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PD-L1 (Programmed death ligand 1)
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PD-L1 expression • PD-L1 negative
1m
MiR-16-5p Promotes the Progression of Esophageal Squamous Cell Carcinoma via Regulating AMPK/mTOR Signaling Pathway. (PubMed, Ann Clin Lab Sci)
miR-16-5p may promote the proliferation, migration, and invasion of ESCC through modulating AMPK/mTOR signaling pathway.
Journal
|
MIR16 (MicroRNA 16)
1m
Targeting c-MET for Endoscopic Detection of Dysplastic Lesions Within Barrett's Esophagus Using EMI-137 Fluorescence Imaging. (PubMed, Clin Cancer Res)
EMI-137 accumulates in dysplastic lesions within BE and in c-MET positive EAC. EMI-137 imaging has potential as a screening and surveillance tool for patients with BE and as a means to detecting dysplasia and EAC.
Journal
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MET (MET proto-oncogene, receptor tyrosine kinase) • IL1B (Interleukin 1, beta)
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MET overexpression • MET expression • MET positive
1m
Cellular communication network 1 promotes CASP2 mRNA expression but suppresses its protein translation in esophageal adenocarcinoma. (PubMed, J Cell Commun Signal)
As a result, CASP2 contributed nothing to CCN1-induced EAC cell apoptosis. On the contrary, CCN1 promoted CASP3, not only in its transcription but also in its translation and activation, which established the basis for CCN1-induced EAC cell apoptosis.
Journal
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RB1 (RB Transcriptional Corepressor 1) • CASP3 (Caspase 3) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • CCN1 (Cellular Communication Network Factor 1) • E2F1 (E2F transcription factor 1)
1m
Neuroendocrine differentiation and serotonin expression in oesophageal adenocarcinomas after neoadjuvant therapy: correlation with clinicopathological features and outcome. (PubMed, Histopathology)
Our findings support NED as independent predictor of OS in EAC after neoadjuvant chemoradiation. While a subset of tumours with NED expressed serotonin, this did not provide additional prognostic information.
Journal
|
SYP (Synaptophysin)
1m
MET amplification correlates with poor prognosis and immunotherapy response as a subtype of melanoma: a multicenter retrospective study. (PubMed, BMC Cancer)
This database analysis showed that the main type of MET mutation is amplification in malignant melanoma. MET-amplified solid tumors might be considered for targeted therapy, as MET amplification can be regarded as a risk factor affecting the prognosis of patients with tumors treated with immunotherapy.
Retrospective data • Journal • IO biomarker
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MET (MET proto-oncogene, receptor tyrosine kinase)
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MET amplification
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MSK-IMPACT
1m
MEMENTO: Metformin as a Metabolic Intervention in Oesophageal Adenocarcinomas to Improve Response to Neoadjuvant Chemoradiotherapy (clinicaltrials.gov)
P2, N=14, Not yet recruiting, Amsterdam UMC, location VUmc
New P2 trial
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CD163 (CD163 Molecule)
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carboplatin • metformin
1m
Multi-Site Detection of Barrett's Esophagus in Patients Without Chronic GERD Symptoms (clinicaltrials.gov)
P=N/A, N=800, Not yet recruiting, Case Comprehensive Cancer Center
New trial
|
VIM (Vimentin) • CCNA1 (Cyclin A1)
1m
REACT: Rapid Assessment of Esophageal Adenocarcinoma Risk Test (clinicaltrials.gov)
P=N/A, N=51, Terminated, Columbia University | N=100 --> 51 | Suspended --> Terminated; Product recall
Enrollment change • Trial termination
1m
Bemarituzumab in FGFR2b+ Patients With Advanced or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction, Who Failed at Least One Prior Line of Palliative Chemotherapy (clinicaltrials.gov)
P2, N=126, Not yet recruiting, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
New P2 trial • Metastases
|
paclitaxel • Cyramza (ramucirumab) • irinotecan • Lonsurf (trifluridine/tipiracil) • bemarituzumab (AMG 552)
1m
Synergistic Effects of PD-1 Antibody and Chemotherapy Followed by Surgeon-led Local Treatment in Patients with Limited-metastatic Gastric Cancer (ROSETTE) (clinicaltrials.gov)
P2, N=82, Not yet recruiting, Shanghai Zhongshan Hospital | Trial completion date: Jul 2028 --> Dec 2028 | Initiation date: Jul 2024 --> Nov 2024 | Trial primary completion date: Jul 2027 --> Dec 2027
Trial completion date • Trial initiation date • Trial primary completion date • Metastases
|
Opdivo (nivolumab) • Tyvyt (sintilimab) • Tevimbra (tislelizumab-jsgr) • capecitabine • oxaliplatin
1m
Liquid-liquid phase separation-related signature predicts prognosis and therapeutic response in esophageal adenocarcinoma. (PubMed, Anal Chim Acta)
Liquid-liquid phase separation is potentially implicated in esophageal adenocarcinoma and works as a prognostic biomarker assessment of vulnerability to LLPS, which could help develop individualized therapies by showing how one is situated about various medications where responses vary across the body.
Journal • Tumor mutational burden
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TMB (Tumor Mutational Burden)
2ms
A clinical trial to determine the safety and tolerability of GRWD5769 in combination with anticancer treatments in patients with solid malignancies. (ACTRN12623001077651)
P1, N=36, Recruiting, Grey Wolf Therapeutics Pty Ltd | Not yet recruiting --> Recruiting
Enrollment open
|
Libtayo (cemiplimab-rwlc) • GRWD5769
2ms
A Phase I Study of [177Lu]Lu-FF58 in Patients With Advanced Solid Tumors. (clinicaltrials.gov)
P1, N=6, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting | N=116 --> 6
Enrollment closed • Enrollment change • Metastases
2ms
OPERARADIO: Organ-Preserving Endoscopic Resection & Adjuvant RADIO-immuno-chemotherapy for Esophageal Cancer (clinicaltrials.gov)
P1, N=11, Active, not recruiting, University of Manitoba | Recruiting --> Active, not recruiting | Trial completion date: Jun 2026 --> Jul 2029 | Trial primary completion date: Jun 2024 --> Jul 2025
Enrollment closed • Trial completion date • Trial primary completion date
2ms
Evaluate Mesothelin as a Biomarker for the Clinical Management of Esophageal Adenocarcinoma (EAC) (clinicaltrials.gov)
P=N/A, N=371, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Sep 2025 --> Oct 2024 | Trial primary completion date: Sep 2025 --> Oct 2024
Trial completion • Trial completion date • Trial primary completion date
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MSLN (Mesothelin)
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MSLN expression
2ms
Evolving Treatment Landscape for Advanced Esophageal and Gastroesophageal Junction Adenocarcinoma. (PubMed, Curr Oncol Rep)
The approaches to these targets may act together, in sequence, and even synergistically to improve outcomes. Herein, we review the state of the field, including highlighting ongoing clinical trials and additional emerging agents and approaches.
Review • Journal • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • CLDN18 (Claudin 18)
2ms
FOXP3+/CD8+ ratio associated with aggressive behavior in RUNX3-methylated diffuse esophagogastric junction tumor. (PubMed, Cancer Sci)
Multiomics data from The Cancer Genome Atlas linked CCL28 with RUNX3-suppressed diffuse histological subtypes of non-EBV/non-MSI-high GEA. Our data suggest that a high FOXP3+/CD8+ ratio at the invasive margin might indicate tumor immune escape via CCL28, particularly in the RUNX3-methylated diffuse histological subtype.
Journal • MSi-H Biomarker
|
MSI (Microsatellite instability) • CD8 (cluster of differentiation 8) • FOXP3 (Forkhead Box P3) • RUNX3 (RUNX Family Transcription Factor 3)
|
CD8 expression • FOXP3 expression
2ms
Study of INBRX-105 and INBRX-105 With Pembrolizumab in Patients With Solid Tumors Including Head and Neck Cancer (clinicaltrials.gov)
P1, N=160, Terminated, Inhibrx Biosciences, Inc | Trial completion date: Dec 2025 --> Oct 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Aug 2025 --> Oct 2024; Program terminated due to lack of meaningful efficacy signal.
Trial completion date • Trial termination • Trial primary completion date • Combination therapy • Metastases
|
TMB (Tumor Mutational Burden)
|
TMB-H
|
Keytruda (pembrolizumab) • enristomig (INBRX-105)
2ms
DKN-01 in Combination With Tislelizumab and Chemotherapy as First-Line Therapy in Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: DisTinGuish. (PubMed, J Clin Oncol)
DKN-01 can be safely combined with frontline fluoropyrimidine/oxaliplatin and tislelizumab and demonstrates encouraging activity independent of PD-L1 expression levels. A randomized phase II trial is ongoing (ClinicalTrials.gov identifier: NCT04363801).
Journal • Combination therapy • PD(L)-1 Biomarker • IO biomarker • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • DKK1 (dickkopf WNT signaling pathway inhibitor 1)
|
PD-L1 expression • HER-2 negative
|
Tevimbra (tislelizumab-jsgr) • capecitabine • oxaliplatin • sirexatamab (DKN-01)
2ms
Immune checkpoint inhibitors in advanced gastroesophageal adenocarcinoma: a series of patient-level meta-analyses in different programmed death-ligand 1 subgroups. (PubMed, ESMO Open)
In PD-L1low HER-2 negative GEAC, the benefit of first-line ICI is modest, yet significant. Further translational work is warranted to better select patients who could benefit from immunotherapy in this setting. Meanwhile, alternative therapeutic options such as zolbetuximab in Claudin18.2-positive disease must be taken into account.
Clinical • Journal • Checkpoint inhibition • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • CLDN18 (Claudin 18)
|
HER-2 negative • PD-L1-L • HER-2 negative + CLDN18.2 positive
|
Vyloy (zolbetuximab-clzb)
2ms
High levels of autotaxin and lysophosphatidic acid predict poor outcome in treatment of resectable gastric carcinoma. (PubMed, Eur J Cancer)
Based on these observations, clinical trials with ATX-targeted drugs and standard chemotherapy regimens may benefit from selecting GEA patients based on their levels of ATX, LPA and CEA.
Journal
|
ENPP2 (Ectonucleotide Pyrophosphatase/Phosphodiesterase 2)
2ms
The use of immune checkpoint inhibitors in advanced gastric/gastroesophageal adenocarcinomas - real-world evidence and the use of alternative dosing. (PubMed, Ecancermedicalscience)
Seventy-four patients (81%) received nivolumab, while the remaining received pembrolizumab. Patients with advanced G/GEJ adenocarcinomas in the real world predominantly received ICIs during later lines of therapy as opposed to first line therapy. Using a CPS cutoff of ≥5 as opposed to CPS <5 predicts for improved survivals in MSS patients and patients receiving low dose ICIs have similar survival outcomes to patients receiving standard dose ICIs within the confines of a heterogenous study cohort.
Journal • HEOR • Checkpoint inhibition • Real-world evidence • Real-world • Metastases
|
MSI (Microsatellite instability)
|
MSI-H/dMMR
|
Keytruda (pembrolizumab) • Opdivo (nivolumab)
2ms
ZWI-ZW25-201: A Safety and Efficacy Study of ZW25 (Zanidatamab) Plus Combination Chemotherapy in HER2-expressing Gastrointestinal Cancers, Including Gastroesophageal Adenocarcinoma, Biliary Tract Cancer, and Colorectal Cancer (clinicaltrials.gov)
P2, N=74, Active, not recruiting, Jazz Pharmaceuticals | Trial primary completion date: Aug 2024 --> Jul 2025
Trial primary completion date
|
HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • RAS (Rat Sarcoma Virus)
|
HER-2 amplification • HER-2 expression • KRAS wild-type • BRAF wild-type • NRAS wild-type
|
Avastin (bevacizumab) • cisplatin • gemcitabine • 5-fluorouracil • capecitabine • oxaliplatin • leucovorin calcium • Ziihera (zanidatamab-hrii)
2ms
Targeting esophageal carcinoma: molecular mechanisms and clinical studies. (PubMed, MedComm (2020))
The discussion extends to evaluating combination therapies, spotlighting the synergy between targeted and immune-mediated treatments, and introduces the burgeoning domain of antibody-drug conjugates, bispecific antibodies, and multitarget-directed ligands. This review lies in its holistic synthesis of EC's molecular underpinnings and therapeutic interventions, fused with an outlook on future directions including overcoming resistance mechanisms, biomarker discovery, and the potential of novel drug formulations.
Review • Journal • IO biomarker
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
2ms
A Study to Evaluate the Safety of INCA33890 in Participants With Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
P1, N=245, Recruiting, Incyte Corporation | N=165 --> 245
Enrollment change • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • PGR (Progesterone receptor) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
HER-2 negative • ER negative • PGR negative
|
INCA33890
2ms
Expression of Trefoil Factor 1 (TFF1) in Cancer: A Tissue Microarray Study Involving 18,878 Tumors. (PubMed, Diagnostics (Basel))
The link between TFF1 expression and parameters of malignancy argues for a relevant biological role of TFF1 in cancer. TFF1 may represent a suitable therapeutic target due to its expression in only a few normal cell types.
Journal
|
PGR (Progesterone receptor) • TFF1 (Trefoil Factor 1)
|
PGR expression
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