Episode # 3 • 17 Jan 2025
Diagnosis & Management of Advanced HER2-Negative Upper GI Cancers
Five years ago, first-line treatment for advanced HER2-negative gastroesophageal cancer meant chemotherapy; today claudin 18.2, PD-L1, and mismatch repair status shape the plan, often for a patient who cannot afford to wait for the results. On this episode of the BackTable GI Oncology Creator Weekend™, host Dr. Kate Baker interviews medical oncologists Dr. Ronan Hsieh and Dr. Dani Castillo about the diagnosis and management of advanced HER2-negative upper GI cancers. They discuss the biomarker workup at diagnosis, next-generation sequencing and liquid biopsy, when to biopsy metastatic sites, and why both guests start chemotherapy before every result is available.
Timestamps
00:00 - Introduction
01:32 - Diagnosis and Biomarker Testing
04:25 - Circulating Tumor DNA
06:31 - Starting Chemotherapy Before Biomarker Results
09:10 - First-Line Therapy and Zolbetuximab Toxicity
14:46 - Sequencing Therapy in Double Expressors
21:11 - Clinical Trials and Emerging Targets
24:54 - Immunotherapy Eligibility and Autoimmune Disease
29:26 - Obstruction, Bleeding, and Multidisciplinary Care
32:30 - Supportive Care
36:50 - Future Directions
39:36 - Organ Preservation and Closing Remarks
Resources
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More about this episode
The conversation covers first-line therapy based on the SPOTLIGHT, GLOW, and CheckMate 649 trials, practical strategies for the nausea and vomiting that come with zolbetuximab, and how to sequence treatment when a tumor is positive for both claudin 18.2 and PD-L1, including the ILUSTRO cohort 4 data and the ongoing LUCERNA trial. Dr. Hsieh and Dr. Castillo make the case for offering clinical trials early, discuss immunotherapy in patients with autoimmune disease, and explain how stents, feeding tubes, and palliative radiation help manage obstruction and bleeding. They close on supportive care, from palliative medicine and dietitians to social work and psycho-oncology, and on organ preservation in mismatch repair-deficient disease, a reminder that caring for these patients takes a whole team.
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