Standard-of-Care, Second-Line, and Future Therapies for GEJ and Esophageal Adenocarcinoma

ASCO 2024: What the ESOPEC, RENAISSANCE, and ARMANI Trials Mean for the Future of Esophageal Cancer Treatment

Drs Samuel Klempner and Yelena Janjigian break down major takeaways from the clinical trial data presented at ASCO 2024. Relevant disclosures can be found with the episode show notes on Medscape https://www.medscape.com/viewarticle/999887. The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Esophageal Cancer https://emedicine.medscape.com/article/277930-overview Ten-Year Outcome of Neoadjuvant Chemoradiotherapy Plus Surgery for Esophageal Cancer: The Randomized Controlled CROSS Trial https://pubmed.ncbi.nlm.nih.gov/33891478/ Prospective Randomized Multicenter Phase III Trial Comparing Perioperative Chemotherapy (FLOT Protocol) to Neoadjuvant Chemoradiation (CROSS Protocol) in Patients With Adenocarcinoma of the Esophagus (ESOPEC Trial). https://ascopubs.org/doi/10.1200/JCO.2024.42.17_suppl.LBA1 The RENAISSANCE (AIO-FLOT5) Trial: Effect of Chemotherapy Alone vs. Chemotherapy Followed by Surgical Resection on Survival and Quality of Life in Patients With Limited-Metastatic Adenocarcinoma of the Stomach or Esophagogastric Junction – A Phase III Trial of the German AIO/CAO-V/CAOGI https://pubmed.ncbi.nlm.nih.gov/29282088/ MATTERHORN: Phase III Study of Durvalumab Plus FLOT Chemotherapy in Resectable Gastric/Gastroesophageal Junction Cancer https://pubmed.ncbi.nlm.nih.gov/35535555/ First-Line Nivolumab Plus Chemotherapy vs Chemotherapy Alone for Advanced Gastric, Gastro-oesophageal Junction, and Oesophageal Adenocarcinoma (CheckMate 649): A Randomised, Open-Label, Phase 3 Trial https://pubmed.ncbi.nlm.nih.gov/34102137/ Pembrolizumab Plus Trastuzumab and Chemotherapy for HER2-Positive Gastric or Gastro-oesophageal Junction Adenocarcinoma: Interim Analyses From the Phase 3 KEYNOTE-811 Randomised Placebo-Controlled Trial https://pubmed.ncbi.nlm.nih.gov/37871604/ Assessment of Ramucirumab Plus Paclitaxel as Switch Maintenance Versus Continuation of First-Line Chemotherapy in Patients With Advanced HER-2 Negative Gastric or Gastroesophageal Junction Cancers: The ARMANI Phase III Trial https://pubmed.ncbi.nlm.nih.gov/30922323/

Emerging Biomarkers and Novel Therapies for Esophageal Cancer

Drs Samuel Klempner and Haeseong Park discuss emerging biomarkers and novel therapies for esophageal cancer, including new data from ASCO. Relevant disclosures can be found with the episode show notes on Medscape https://www.medscape.com/viewarticle/999886. The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Esophageal Cancer https://emedicine.medscape.com/article/277930-overview Prospective Randomized Multicenter Phase III Trial Comparing Perioperative Chemotherapy (FLOT Protocol) to Neoadjuvant Chemoradiation (CROSS Protocol) in Patients With Adenocarcinoma of the Esophagus (ESOPEC Trial) https://ascopubs.org/doi/pdf/10.1200/JCO.2024.42.17_suppl.LBA1 Clinical Utility of the Combined Positive Score for Programmed Death Ligand-1 Expression and the Approval of Pembrolizumab for Treatment of Gastric Cancer https://pubmed.ncbi.nlm.nih.gov/30028179/ Pembrolizumab Plus Chemotherapy Versus Placebo Plus Chemotherapy for HER2-Negative Advanced Gastric Cancer (KEYNOTE-859): A Multicentre, Randomised, Double-Blind, Phase 3 Trial https://pubmed.ncbi.nlm.nih.gov/37875143/ 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 https://pubmed.ncbi.nlm.nih.gov/34102137/ FOLFIRINOX for the Treatment of Advanced Gastroesophageal Cancers: A Phase 2 Nonrandomized Clinical Trial https://pubmed.ncbi.nlm.nih.gov/32469386/ Targeting CLDN18.2 in Cancers of the Gastrointestinal Tract: New Drugs and New Indications https://pubmed.ncbi.nlm.nih.gov/36969060/ Targeting FGFR2 Positive Gastroesophageal Cancer: Current and Clinical Developments https://pubmed.ncbi.nlm.nih.gov/36238135/ The KEYNOTE-811 Trial of Dual PD-1 and HER2 Blockade in HER2-Positive Gastric Cancer https://pubmed.ncbi.nlm.nih.gov/34912120/ Dose-Escalation and Dose-Expansion Study of Trastuzumab Deruxtecan (T-DXd) Monotherapy and Combinations in Patients (pts) With Advanced/Metastatic HER2+ Gastric Cancer (GC)/Gastroesophageal Junction Adenocarcinoma (GEJA): DESTINY-Gastric03 https://ascopubs.org/doi/10.1200/JCO.2022.40.4_suppl.295 Co-inhibition of TIGIT and PD-1/PD-L1 in Cancer Immunotherapy: Mechanisms and Clinical Trials https://pubmed.ncbi.nlm.nih.gov/37291608/ 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 https://pubmed.ncbi.nlm.nih.gov/37068504/ The RENAISSANCE (AIO-FLOT5) Trial: Effect of Chemotherapy Alone vs. Chemotherapy Followed by Surgical Resection on Survival and Quality of Life in Patients With Limited-Metastatic Adenocarcinoma of the Stomach or Esophagogastric Junction - a Phase III Trial of the German AIO/CAO-V/CAOGI https://pubmed.ncbi.nlm.nih.gov/29282088/

Clinical Scenarios and Approaches to Treating Locally Advanced Esophageal Adenocarcinoma

Drs Samuel Klempner and Nataliya Uboha discuss the treatment of patients with locally advanced esophageal adenocarcinomas who opt to not undergo esophagostomy. Relevant disclosures can be found with the episode show notes on Medscape https://www.medscape.com/viewarticle/999885. The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Esophageal Cancer https://emedicine.medscape.com/article/277930-overview Ten-Year Outcome of Neoadjuvant Chemoradiotherapy Plus Surgery for Esophageal Cancer: The Randomized Controlled CROSS Trial https://pubmed.ncbi.nlm.nih.gov/33891478/ A Review of Circulating Tumor DNA in the Diagnosis and Monitoring of Esophageal Cancer https://pubmed.ncbi.nlm.nih.gov/35210388/ Predictive Value of PD-L1 Expression in Response to Immune Checkpoint Inhibitors for Esophageal Cancer Treatment: A Systematic Review and Meta-analysis https://pubmed.ncbi.nlm.nih.gov/36591463/ Phase III, Randomised Trial of Avelumab Versus Physician's Choice of Chemotherapy as Third-line Treatment of Patients With Advanced Gastric or Gastro-esophageal Junction Cancer: Primary Analysis of JAVELIN Gastric 300 https://pubmed.ncbi.nlm.nih.gov/30052729/ Assessment of Ramucirumab Plus Paclitaxel as Switch Maintenance Versus Continuation of First-line Chemotherapy in Patients With Advanced HER2-Negative Gastric or Gastroesophageal Junction Cancers: The ARMANI Phase III Trial https://pubmed.ncbi.nlm.nih.gov/30922323/ Study Protocol for the OligoMetastatic Esophagogastric Cancer (OMEC) Project: A Multidisciplinary European Consensus Project on the Definition and Treatment for Oligometastatic Esophagogastric Cancer https://pubmed.ncbi.nlm.nih.gov/36184420/ The RENAISSANCE (AIO-FLOT5) Trial: Effect of Chemotherapy Alone vs. Chemotherapy Followed by Surgical Resection on Survival and Quality of Life in Patients With Limited-Metastatic Adenocarcinoma of the Stomach or Esophagogastric Junction - a Phase III Trial of the German AIO/CAO-V/CAOGI https://pubmed.ncbi.nlm.nih.gov/29282088/ EA2183: A Phase III Study of Consolidative Radiotherapy in Patients With Oligometastatic HER2-Negative Esophageal and Gastric Adenocarcinoma https://ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.TPS4162

Navigating Esophageal Squamous Cell Cancer From Diagnosis to Treatment

Drs Samuel Klempner and Geoffrey Ku deep dive into all things esophageal squamous cell cancer, including detection, staging, and treatment. Relevant disclosures can be found with the episode show notes on Medscape https://www.medscape.com/viewarticle/999884. The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Preoperative Chemoradiotherapy for Esophageal or Junctional Cancer https://pubmed.ncbi.nlm.nih.gov/22646630/ Chemoradiotherapy of Locally Advanced Esophageal Cancer: Long-Term Follow-up of a Prospective Randomized Trial (RTOG 85-01). Radiation Therapy Oncology Group https://pubmed.ncbi.nlm.nih.gov/10235156/ Definitive Chemoradiotherapy With FOLFOX Versus Fluorouracil and Cisplatin in Patients With Oesophageal Cancer (PRODIGE5/ACCORD17): Final Results of a Randomised, Phase 2/3 Trial https://pubmed.ncbi.nlm.nih.gov/24556041/ Randomized Study on Dose Escalation in Definitive Chemoradiation for Patients With Locally Advanced Esophageal Cancer (ARTDECO Study) https://pubmed.ncbi.nlm.nih.gov/34101496/ 18-Fluorodeoxy-Glucose Positron Emission Computed Tomography as Predictive of Response After Chemoradiation in Oesophageal Cancer Patients https://pubmed.ncbi.nlm.nih.gov/26321501/ Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer https://pubmed.ncbi.nlm.nih.gov/33789008/ Predictive Value of PD-L1 Expression in Response to Immune Checkpoint Inhibitors for Esophageal Cancer Treatment: A Systematic Review and Meta-analysis https://pubmed.ncbi.nlm.nih.gov/36591463/ Association of PD-L1 Expression and Other Variables With Benefit From Immune Checkpoint Inhibition in Advanced Gastroesophageal Cancer: Systematic Review and Meta-analysis of 17 Phase 3 Randomized Clinical Trials https://pubmed.ncbi.nlm.nih.gov/36006624/ A Randomized Controlled Phase III Trial Comparing Two Chemotherapy Regimen and Chemoradiotherapy Regimen as Neoadjuvant Treatment for Locally Advanced Esophageal Cancer, JCOG1109 NExT Study https://ascopubs.org/doi/10.1200/JCO.2022.40.4_suppl.238 Delayed Surgical Intervention After Chemoradiotherapy in Esophageal Cancer: (DICE) Study https://pubmed.ncbi.nlm.nih.gov/37477039/ Initial Safety Assessment of the Endoscopically Injected Oncolytic Virus OBP-301 in Medically Inoperable Esophageal Cancer: NRG-GI007 https://ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.341 A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Multicenter, Global Study of Durvalumab With and After Chemoradiotherapy in Patients With Locally Advanced, Unresectable Esophageal Squamous Cell Carcinoma: KUNLUN https://ascopubs.org/doi/10.1200/JCO.2022.40.4_suppl.TPS373 KEYNOTE-975 Study Design: A Phase III Study of Definitive Chemoradiotherapy Plus Pembrolizumab in Patients With Esophageal Carcinoma https://pubmed.ncbi.nlm.nih.gov/33533655/ KEYNOTE-590: Phase III Study of First-Line Chemotherapy With or Without Pembrolizumab for Advanced Esophageal Cancer https://pubmed.ncbi.nlm.nih.gov/30735435/ Nivolumab Combination Therapy in Advanced Esophageal Squamous-Cell Carcinoma https://pubmed.ncbi.nlm.nih.gov/35108470/

Standard-of-Care, Second-Line, and Future Therapies for GEJ and Esophageal Adenocarcinoma

Drs Samuel Klempner and Zev Wainberg discuss standard-of-care, second-line, and future therapies for GE junction, esophageal, and gastric cancers. Relevant disclosures can be found with the episode show notes on Medscape https://www.medscape.com/viewarticle/999883. The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Esophageal Cancer https://emedicine.medscape.com/article/277930-overview Scoring Systems for PD-L1 Expression and Their Prognostic Impact in Patients With Resectable Gastric Cancer https://pubmed.ncbi.nlm.nih.gov/33098489/ Assessment of Ramucirumab Plus Paclitaxel as Switch Maintenance Versus Continuation of First-Line Chemotherapy in Patients With Advanced HER-2 Negative Gastric or Gastroesophageal Junction Cancers: The ARMANI Phase III Trial https://pubmed.ncbi.nlm.nih.gov/30922323/ Clinical Circulating Tumor DNA Testing for Precision Oncology https://pubmed.ncbi.nlm.nih.gov/36915242/ Mismatch Repair-Deficient Colorectal Cancer: Building on Checkpoint Blockade https://pubmed.ncbi.nlm.nih.gov/35649217/ The KEYNOTE-811 Trial of Dual PD-1 and HER2 Blockade in HER2-Positive Gastric Cancer https://pubmed.ncbi.nlm.nih.gov/34912120/ Trastuzumab Deruxtecan for Subjects With HER2-Positive Gastric Cancer or Gastro-Esophageal Junction Adenocarcinoma After Progression on or After a Trastuzumab-Containing Regimen (DESTINY-Gastric04) https://clinicaltrials.gov/study/NCT04704934 Challenges and Therapeutic Opportunities in the dMMR/MSI-H Colorectal Cancer Landscape https://pubmed.ncbi.nlm.nih.gov/36831367/ An Introduction to the Performance of Immunohistochemistry https://pubmed.ncbi.nlm.nih.gov/30539453/ Anti-TIGIT Therapies for Solid Tumors: A Systematic Review https://pubmed.ncbi.nlm.nih.gov/36933320/ LAG-3 as the Third Checkpoint Inhibitor https://pubmed.ncbi.nlm.nih.gov/37488429/ Novel WRN Helicase Inhibitors Selectively Target Microsatellite Unstable Cancer Cells https://pubmed.ncbi.nlm.nih.gov/38587317/ Fruquintinib Plus Paclitaxel Versus Paclitaxel as Second-Line Therapy for Patients With Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (FRUTIGA): A Randomized, Multicenter, Double-Blind, Placebo-Controlled, Phase 3 Study https://ascopubs.org/doi/10.1200/JCO.2024.42.36_suppl.438780 Targeting FGFR2 Positive Gastroesophageal Cancer: Current and Clinical Developments https://pubmed.ncbi.nlm.nih.gov/36238135/ Bemarituzumab in Patients With FGFR2b-Selected Gastric or Gastro-Oesophageal Junction Adenocarcinoma (FIGHT): A Randomised, Double-Blind, Placebo-Controlled, Phase 2 Study https://pubmed.ncbi.nlm.nih.gov/36244398/ Optimism Surrounds Claudin 18.2 ADC https://pubmed.ncbi.nlm.nih.gov/37975577/ Methionine Adenosyltransferases in Cancers: Mechanisms of Dysregulation and Implications for Therapy https://pubmed.ncbi.nlm.nih.gov/29141455/