Clinical Investigator Perspectives on the Management of Patients with Gastroesophageal Cancers (Part 2 of a 3-Part Series) (ASCO-GI 2022)
MODULE 1: Current and Future Front-Line Management of Advanced Gastric and Gastroesophageal Junction (GEJ) Cancer Available efficacy and safety results from the Phase III CheckMate 649 study comparing first-line nivolumab in combination with chemotherapy or ipilimumab to chemotherapy alone for advanced gastric/GEJ adenocarcinoma; FDA approval and patient selection for up-front nivolumab/chemotherapy Mechanism of action of sintilimab; recently presented results from the Phase III ORIENT-16 trial comparing sintilimab with chemotherapy to chemotherapy alone as first-line treatment Biologic rationale for targeting claudin 18.2 in gastric/GEJ cancers; mechanism of antitumor activity of zolbetuximab Available efficacy and safety findings with first-line zolbetuximab/chemotherapy in patients with advanced claudin 18.2-positive gastric/GEJ adenocarcinoma; ongoing Phase III SPOTLIGHT and GLOW studies Frequency of FGFR2b overexpression in gastroesophageal cancers; mechanism of action of bemarituzumab Major efficacy and safety data from the Phase II FIGHT trial evaluating bemarituzumab/chemotherapy versus chemotherapy alone as first-line therapy for patients with FGFR2b-positive metastatic gastric/GEJ cancer; FDA breakthrough therapy designation MODULE 2: Contemporary Management of HER2-Positive Advanced Gastric and GEJ Cancer Principal outcomes from the Phase III KEYNOTE-811 trial supporting the FDA approval of first-line pembrolizumab/trastuzumab/chemotherapy for metastatic HER2-positive disease Updated results, including overall survival outcomes, from the Phase II DESTINY-Gastric01 study of trastuzumab deruxtecan (T-DXd) for patients with progressive HER2-positive gastric/GEJ cancer FDA approval of T-DXd for patients with HER2-positive gastric/GEJ cancer who have previously received a trastuzumab-based regimen; optimal incorporation into routine practice Recently presented efficacy and safety findings from the Phase II DESTINY-Gastric02 trial evaluating T-DXd in Western patients with HER2-positive gastric/GEJ cancer previously treated with a trastuzumab-based regimen Ongoing studies with T-DXd in earlier lines of treatment and/or in combination with other systemic therapies MODULE 3: Selection and Sequencing of Therapy for Relapsed Gastric and GEJ Cancer Optimal integration of ramucirumab into current clinical algorithms for metastatic gastric/GEJ cancer Available data with and ongoing investigation of novel ramucirumab-combination regimens Clinical research supporting the use of TAS-102 for heavily pretreated metastatic gastric/GEJ cancer; patient selection for treatment with TAS-102 Current role, if any, of anti-PD-1 monotherapy for patients with recurrent metastatic gastric/GEJ cancer; clinical implications of the voluntary withdrawal of third-line pembrolizumab Other promising agents and strategies under investigation for advanced gastric/GEJ cancer MODULE 4: Key Findings Informing the Treatment of Localized and Advanced Esophageal Cancer Design, eligibility criteria and primary findings from the Phase III KEYNOTE-590 study leading to the FDA approval of first-line pembrolizumab/chemotherapy for advanced esophageal and GEJ cancer; patient selection for this approach Major findings from the Phase III CheckMate 648 study evaluating nivolumab/chemotherapy, nivolumab/ipilimumab and chemotherapy alone for patients with unresectable advanced or metastatic squamous cell carcinoma of the esophagus Available Phase III clinical trial findings (eg, JUPITER-06, ORIENT-15) with investigational anti-PD-1 antibodies with chemotherapy as first-line treatment for esophageal squamous cell carcinoma Key efficacy and safety outcomes from the Phase III CheckMate 577 study of adjuvant nivolumab for patients with resected esophageal or GEJ cancer; recent FDA approval and appropriate integration into management algorithms
