SOBRE ESTE EPISÓDIO
When a gastroesophageal tumor is positive for HER2, PD-L1, and claudin 18.2, which target should you treat first and how do you decide? On this episode of the BackTable GI Oncology Creator Weekend™, host Dr. Kate Baker interviews Dr. Geoffrey Buckle, a GI medical oncologist at UCSF, and Dr. Ronan Hsieh, a GI oncologist at Swedish Cancer Institute in Seattle, for a breakdown of therapy selection and management in advanced HER2-positive upper GI cancers. They start with a detailed case, covering biomarker workup, how to choose a first-line regimen without head-to-head data, and how to manage nutrition and palliative radiation when a patient presents with dysphagia and weight loss.
---
Get the BackTable app
https://www.backtable.com/app
---
Timestamps
00:00 - Introduction
01:41 - Case Presentation and Biomarker Workup
05:07 - First-Line Treatment Selection
11:27 - Oligoprogressive Disease and Local Therapy
16:02 - HER2 Testing and Tumor Heterogeneity
20:19 - ctDNA in Upper GI Cancers
22:27 - HERIZON-GEA-01 and Zanidatamab
27:18 - Triplet Versus Doublet and Diarrhea Management
29:17 - Second-Line Therapy and Rebiopsy
32:33 - Trastuzumab Deruxtecan and Interstitial Lung Disease
36:33 - Later-Line Options and HER2-Low Disease
39:17 - Future Directions and Closing Remarks
---
More about this episode
The conversation expands to interpreting equivocal HER2 results, tumor heterogeneity, and the importance of a second pathology review before committing to a treatment strategy. Dr. Hsieh explains how he approaches the HERIZON-GEA-01 trial data and the need to manage triplet therapy toxicity, especially diarrhea. The group discusses second-line rebiopsy to confirm HER2 status, the role of circulating tumor DNA (ctDNA), counseling and monitoring for interstitial lung disease on antibody-drug conjugates, and what to do for HER2 IHC 2+ FISH-negative tumors. They close with future directions, including trials moving HER2-directed therapies into earlier disease, the challenge of limited therapy lines, and why every line counts in this patient population.
---
Resources
Shitara K, et al. Zanidatamab with and without Tislelizumab in HER2-Positive Gastroesophageal Cancer (HERIZON-GEA-01). N Engl J Med. 2026
https://pubmed.ncbi.nlm.nih.gov/42202319/
FDA approves zanidatamab-hrii and tislelizumab-jsgr for HER2-positive gastric, gastroesophageal junction and esophageal adenocarcinoma (August 2026)
https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-zanidatamab-hrii-and-tislelizumab-jsgr-her2-positive-gastric-gastroesophageal-junction
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. Lancet. 2023
https://pubmed.ncbi.nlm.nih.gov/37871604/
Trastuzumab in combination with chemotherapy versus chemotherapy alone for HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA). Lancet. 2010
https://pubmed.ncbi.nlm.nih.gov/20728210/
Trastuzumab Deruxtecan in HER2-Low Gastric or Gastroesophageal Junction Adenocarcinoma: Exploratory Cohort Results in a Phase II Trial (DESTINY-Gastric01). J Clin Oncol. 2023
https://pubmed.ncbi.nlm.nih.gov/36379002/
GEMINI-PeriOp GC: Novel Agents or Combinations as Perioperative Treatment in Locally Advanced Resectable Gastroesophageal Adenocarcinoma (trial record)
https://clinicaltrials.gov/study/NCT07069712
Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat Med. 2023
https://pubmed.ncbi.nlm.nih.gov/37524953/
Perioperative Durvalumab in Gastric and Gastroesophageal Junction Cancer (MATTERHORN). N Engl J Med. 2025
https://pubmed.ncbi.nlm.nih.gov/40454643/
NCCN Clinical Practice Guidelines in Oncology: Gastric Cancer and Esophageal and Esophagogastric Junction Cancers (current versions)
https://www.nccn.org/guidelines/category_1
Dr. Geoffrey Buckle, UCSF Health physician profile
https://www.ucsfhealth.org/providers/geoffrey-buckle
Dr. Ronan Hsieh, Swedish physician profile
https://www.swedish.org/doctors/medical-oncology/wa/seattle/ronan-hsieh-1457880031
Dr. Kate Baker, BackTable Tumor Board contributor page
https://www.backtable.com/shows/tumor-board/contributors/dr-kate-baker
---
BackTable Tumor Board is the go-to multidisciplinary podcast for medical oncologists, surgical oncologists, and other healthcare professionals that play an active role in cancer care.
Download the free BackTable app to get early access to new episodes, cases, and courses curated by physicians in your specialty.
► https://www.backtable.com/app
