Immunotherapy and Targeted Therapy for Advanced Gastroesophageal Cancers — Microlearning Activity 2: Proceedings from a Session Held Adjunct to the 2026 ASCO GI Cancers Symposium
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This microlearning episode from the 2026 ASCO GI Cancers Symposium features a panel of leading gastroesophageal cancer experts—Dr. Jaffer Ajani, Dr. Rutika Mehta, Dr. John Strickler, and Dr. Sam Klempner—discussing the evolving roles of immunotherapy and targeted therapies in advanced gastroesophageal (GE) cancers. The session centers on real-world clinical cases collected from community oncologists, focusing on treatment sequencing, symptom management, and biomarker prioritization. Key topics include de-escalating antiemetic regimens in well-tolerating patients, managing severe nausea with zolbetuximab (particularly through infusion modifications and lorazepam use), and strategic decisions when patients progress on HER2-targeted therapy. The experts emphasize the importance of biomarker hierarchy—HER2 positivity taking precedence over PD-L1 and Claudin 18.2—when selecting first-line therapy, especially in complex, biomarker-positive cases. They also debate the use of novel combinations like Folfiri with zolbetuximab in refractory settings and the cautious integration of emerging agents such as Illustro (claudin 18.2-targeted) and zanidatumab, despite limited phase 3 data. The discussion underscores the need for personalized, biomarker-driven approaches while acknowledging the practical challenges of treatment toxicity and access. Key takeaways include: (1) Reduce antiemetics after cycle 2 if nausea is controlled; (2) Avoid zolbetuximab loading doses to reduce acute gastritis; (3) Prioritize HER2-targeted therapy (e.g., trastuzumab) over other agents in HER2+ patients; (4) Use Folfiri instead of Folfox in patients with oxaliplatin intolerance; (5) Consider zolbetuximab dose splitting or infusion pauses for severe nausea; (6) Avoid continuing zolbetuximab beyond progression without evidence of benefit; (7) Use immunotherapy only in PD-L1 CPS ≥5 unless clinical urgency demands earlier use; (8) Drop the 5-FU bolus in Folfox when combining with zanidatumab to improve tolerability and response. The overall tone is pragmatic, evidence-informed, and optimistic about future advances, with a strong emphasis on patient-centered decision-making.
De-escalate antiemetics after cycle 2 if nausea is controlled.
Avoid zolbetuximab loading dose to reduce acute gastritis.
Prioritize HER2-targeted therapy over other agents in HER2+ patients.
Use Folfiri instead of Folfox in patients with oxaliplatin intolerance.
Manage zolbetuximab-induced nausea with infusion pauses, dose splitting, or lorazepam.
…and 3 more takeaways available in PodZeus
Introduction and Panel Overview
The episode opens with an introduction to the session from the 2026 ASCO GI Cancers Symposium, moderated by Dr. Sam Klempner. The faculty includes Dr. Jaffer Ajani, Dr. Rutika Mehta, and Dr. John Strickler, who discuss HER2-targeted therapy, Claudin 18.2 targeting, immunotherapy, and novel agents in advanced gastroesophageal cancers.
Managing Nausea in Zolbetuximab Therapy
“I pause the infusion, give them IV fluids, give them medical permite, and then I'm able to resume the infusion, and they're able to complete in most of the cases.”
Treatment Sequencing After Progression on Zolbetuximab
“If you did not have a response to first-line zolbituximab, you're not going to have a response to second-line zolbituximab.”
Biomarker Prioritization and First-Line Therapy
“HER2 positivity as number one. PD-L1 will be number two. Claudine will be number three. And this is just based on the maturity of different data.”
Integrating Novel Agents and Combination Strategies
The panel evaluates the use of emerging agents like Illustro and zanidatumab, noting that while data are promising, they are not yet standard. Experts caution against combining multiple targeted agents without strong evidence, especially in PD-L1 negative patients.
“HER2 positivity as number one. PD-L1 will be number two. Claudine will be number three. And this is just based on the maturity of different data.”
“If you did not have a response to first-line zolbituximab, you're not going to have a response to second-line zolbituximab.”
“The 5-FU bolus does not add much in the way of benefit and add substantial toxicity.”
Host
Guests
Zolbetuximab
product
Folfox
other
HER2
other
PD-L1
other
Dr. Jaffer Ajani
person
Dr. John Strickler
person
Dr. Rutika Mehta
person
Claudin 18.2
other
Folfiri
other
Dr. Sam Klempner
person
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